PSL GRQs
Summarize the steps of chemical transmission
1. Step 1 : Neurotransmitter molecules are packaged into synaptic vesicles . Vesicular transporters concentrate neurotransmitters inside the vesicle using the energy of an H electrochemical gradient .
Explain a capacitor and capacitance .
A capacitor is a device that is capable of storing separated charge . When the capacitor is charged one plates has a charge of + Q and the other plate has a charge of -Q maintains a potential difference ( V ) between the plates Capacitance ( C ) is the magnitude of the charge stored per unit potential difference : C - Q / V .
Contrast the ion permeability and current produced by opening of serotonin receptors , glycine receptors , and GABAA receptors .
As is the case for the AChRs , the 5 - HT3 receptor channels are permeable to cations and thus produce excitatory currents . In contrast , glycine - activated and GABA , channels are permeable to anions such as Cl- and produce inhibitory currents .
Explain why the idealized single channel IV plots for sodium and potassium approximate the shape of the macroscopic peak IV relationships for the positive Vm range .
In this Vm range , both the sodium and potassium channels through which the currents flow are maximally activated at the peaks of their respective time courses . Thus , the macroscopic peak I V relationships are nearly linear in this range , just as they would be for idealized , fully open channels .
macroscopic currents .
Macroscopic currents are due to the activity of a large population of channels sampled from a whole cell
units for conductance
Siemens
Explain how the lipid bilayer acts as a capacitor
The lipid bilayer can maintain a separation of charge
second form of Ohm's law using conductance ( G ) .
V = I / G
units for charge
coulomb
Explain what the Goldman - Hodgkin - Katz ( GHK ) current equation ( right ) tells us .
current carried by a single ion X ( Ix ) through the membrane or the rate of ions moving through the membrane .
units for capacitance
farad
units for electrical work
joule
Explain the rosette arrangement of channel subunits
radial arrangement of subunits or domains around a central pore classified by 3, 4, 5 , or 6 separate subunits or from a number of subunit
Using Coulomb's law , explain why ions cannot easily diffuse across a membrane .
to move a Na + ion from the extracellular to the intracellular fluid without the aid of any proteins , the Na + would have to cross the membrane by " dissolving " in the lipids of the bilayer - energy required to transfer a Na + ion from water ( high e ) to the interior of a phospholipid membrane ( low e ) is -36 kcal / mole . O 60 fold higher than molecular thermal energy at room temperature o probability that an ion would dissolve in the bilayer is essentially zero
increase in K + conductance shifts Vm back toward the K + equilibrium potential ( Ex ) , thereby restoring the original negative resting potential . Thus , the depolarizing and repolarizing phases of the action potential reflect a transient reversal of the ratio of K + / Na +
voltage changes . That is , the magnitude of a cell's voltage change increases proportionally with the size of the stimulus .
What are the two basic strategies animal nervous systems use to improve the conduction properties of nerve fibers ?
( 1 ) Increasing the diameter of the axon , thus decreasing the internal resistance of the cable . ( 2 ) Myelinating the fibers , which increases the electrical insulation around the cable .
Calculate the equilibrium potential and electrochemical driving force for Ca given the following parameters ( round to the nearest whole number ) : Extracellular concentration [ Ca ] .- 2 mM Intracellular concentration [ Ca ] . - 135 nM Membrane Voltage V ..-- 55 mV
+125 mV and -180 mV
From what you remember about the internal and external calcium concentrations and its reversal potential , draw the current - voltage relationship for calcium . Explain what causes the nonlinear behavior of the curve and what is the name given to this relationship in the curve ?
+126 mV reversal potential nonlinear behavior of the IV relationship due to the asymmetric internal and external concentrations of Ca² + Ca² is more concentrated outside than inside inward Ca² + currents will tend to be larger than the outward Ca² + currents . inward rectification
Two determinants of the electrochemical potential energy difference for a charged permeable ion between two compartments.
- chemical potential energy difference (concentration gradient) - electrical potential energy difference (difference in voltage between the two compartments)
Explain how ionic current and driving force are related .
- ionic current depends on the difference between the actual Vm and Ex - ionic current through a given conductance pathway is proportional to the driving force - the proportionality constant is the ionic conductance ( Gx ) : Ix = Gx ( Vm - Ex )
Calculate the equilibrium potential ( round to nearest whole number ) for potassium ( K ) given the following parameters ( show your work ) . Are the concentration gradient and the electrical gradient pushing K in the same or opposite directions ? T 32 ° C 305.16 K R - 8.3145 J mol " K F - 9.6485 x 10 ' C mol Extracellular concentration [ K ] .- 2.5 mM Intracellular concentration [ K ] . - 130 mM Membrane Voltage V. -55 mV
-104 mV Opposite
List the four major types of potassium currents and the five distinct families of channels . responsible for these macroscopic currents .
1. Delayed outward rectifiers 2. Transient outward rectifiers ( A - type currents ) 3. Ca² + -activated K + currents 4. Inward rectifiers 1. Kv channels ( voltage - gated K + channels related to the Shaker family ) 2. Small- and intermediate - conductance Kc , channels ( Ca2 + -calmodulin - activated K + channels ) , including SKca and IKca channels 3. Large conductance Ka channels ( Ca2 + -activated BKca channels and related Na + - and H + - activated K + channels ) 4. Kir channels ( inward - rectifier K + channels )
2. Step 2 : An action potential , which involves voltage - gated Na and K channels , arrives at the presynaptic nerve terminal . 3. Step 3 : Depolarization opens voltage - gated Ca² + channels , which allows Ca² + to enter the presynaptic terminal . 4. Step 4 : The increase in intracellular Ca² + concentration ( [ Ca² + ] ) triggers the fusion of synaptic vesicles with the presynaptic membrane . As a result , packets ( quanta ) of transmitter molecules are released into the synaptic cleft . 5. Step 5 : The transmitter molecules diffuse across the synaptic cleft and bind to specific receptors on the membrane of the postsynaptic cell . 6. Step 6 : The binding of transmitter activates the receptor , which in turn activates the postsynaptic cell . 7. Step 7 : The process is terminated by ( a ) enzymatic destruction of the transmitter ( e.g. , hydrolysis of Ach by acetylcholinesterase ) , ( b ) uptake of transmitter into the presynaptic nerve terminal or into other cells by Na - dependent transport systems , or ( c ) diffusion of the transmitter molecules away from the synapse .
2.
5. K2P channels ( two - pore K + channels ) Explain what effect A - type potassium current has on repetitively spiking neurons . Specifically , what happens to the interval between spikes / spiking frequency when A - type current is small versus when A - type current is large .
A - type potassium currents are activated in the negative Vm range that prevails during the afterhyperpolarizing phase of action potentials . In neurons that spike repetitively , this A - type current can be very important in determining the interval between successive spikes and thus the timing of repetitive action potentials . For example , if the A - type current is small , Vm rises relatively quickly toward the threshold , and consequently the interspike interval is short and the firing frequency is high . However , if the A - type current is large , Vm rises slowly toward the threshold , and therefore the interspike , interval is long and the firing frequency is low .
What does a dendrogram illustrate?
A hypothetical phylogenetic tree of evolutionary relationships of ion channels
Describe the two molecular mechanisms by which ionotropic receptors and metabotropic receptors transduce information
Agonist - gated receptors that are also ion channels are known as jonotropic receptors . Receptors coupled to G proteins are called metabotropic receptors because their activation initiates a metabolic process involving GTP . Jonotropic and metabotropic receptors determine the ultimate functional response to transmitter release . Activation of an jonotropic receptor causes rapid opening of ion channels . This channel activation , in turn , results in depolarization or hyperpolarization of the postsynaptic membrane , depending on the ionic selectivity of the conductance change . Activation of a metabotropic G protein - linked receptor results in the production of active a and By subunits , which initiate a wide variety of cellular responses by direct interaction with either ion channel proteins or other second - messenger effector proteins . By their very nature , ionotropic , receptors mediate fast ionic synaptic responses that occur on a
What is the difference between the actions of an agonists versus an antagonist ?
Agonists activate opening of the channel and antagonists prevent channel activation .
Explain why the voltage dependence of Nat channel gating is dependent on the extracellular Ca² + concentration .
Although Na + channels do not significantly conduct Ca² + ions across the cell membrane , the voltage dependence of Na * channel gating is nevertheless dependent on the extracellular Ca² + concentration . If [ Ca² + ] is progressively increased above the normal physiological level , the voltage activation range of Na + channels progressively shifts to more positive voltages . Similarly , if [ Ca² + ] , is decreased , the voltage activation range is shifted to more negative voltages . This phenomenon has important clinical implications because a negative shift corresponds to a reduced voltage threshold for action potential firing and results in hyperexcitability and spontaneous muscle twitching . Similarly , a positive voltage shift of Na * channel gating corresponds to decreased electrical excitability ( i.e. , the threshold is now farther away from resting Vm ) , resulting in muscle weakness . Thus , metabolic disorders that result in abnormal plasma [ Ca² + ] , s hypoparathyro ( low [ Ca² + ] ) and hyperparathyroidism ( high [ Ca² + ] ) , can cause marked neurological and neuromuscular symptoms . The mechanism of this voltage shift in Na + channel gating by extracellular divalent cations such as Ca² + is thought to involve an alteration in the transmembrane electrical field that is sensed by the channel protein . Presumably , this effect is caused by Ca² + binding or electrostatic screening of negative charges at the membrane surface .
How does increased intracellular calcium lead to neurotransmitter release ?
As Ca² + enters through voltage - gated Ca 2+ channels , located in register with the active zone of the presynaptic membrane , it binds to multiple sites on the C2 domains of synaptotagmin . These Ca² + -bound C2 domains promote the binding of synaptotagmin to acidic phospholipids in the presynaptic membrane and also displace the complexin , thereby reversing the block to fusion . These events trigger the actual membrane fusion event , accompanied by fusion - pore opening and the beginning of transmitter release .
Describe how graded responses and action potentials spread along the membrane from the site of origin .
As the graded response spreads , its magnitude decays exponentially - bc passive loss of electrical current to the medium - electrotonic conduction The amplitude of a propagating action potential does not diminish with distance because excitation of voltage gated channels in adjacent regions of the excitable membrane progressively regenerates the original response
Name the two methods listed in this section of the textbook by which neurotransmitters terminate their action .
At synapses where Ach is released , this removal is accomplished by enzymatic destruction of the neurotransmitter . However , the more general mechanism in the nervous system involves re uptake of the neurotransmitter mediated by specific high - affinity transport systems located in the presynaptic plasma membrane and surrounding glial cells .
What does the mamba snake toxin dendrotoxin block and what effect does it have on the presynaptic terminal and neurotransmitter release ?
Blockade of presynaptic K + channels by dendrotoxin inhibits repolarization of the presynaptic membrane , thereby prolonging the duration of the action potential and facilitating the release of transmitter in response to the entry of extra Ca² + into the nerve terminal .
not only contribute to membrane depolarization also play a role in signal transduction because Ca² + is an important second messenger .
Ca² + channels also play a pivotal role in a special subset of signal - transduction processes known as excitation - contraction coupling and excitation - secretion coupling . Excitation - contraction ( EC ) coupling refers to the process by which an electrical depolarization at the cell membrane leads to cell contraction , such as the contraction of a skeletal muscle fiber . In EC coupling of skeletal muscle , one class of plasma - membrane Ca² + channel that is located in the transverse tubule membrane of skeletal muscle serves as the voltage sensor and forms a direct mechanical linkage to intracellular Ca² + -release channels that are located in the sarcoplasmic reticulum ( SR ) membrane . In contrast , Ca² + channels play a different role in EC coupling in cardiac muscle , where Ca² + channels in the plasma membrane mediate an initial influx of Ca² + . The resultant increase in [ Ca² + ] triggers an additional release of Ca² + stored in the SR by a process known as Ca² + -induced Ca² + release .
Explain why chemical synapses should be considered a unidirectional pathway for signal propagation that can be modulated by bidirectional chemical communication between two interacting cells .
Chemical synapses propagate current in one direction : from the presynaptic cell that releases the transmitter to the postsynaptic cell that contains the receptors that recognize and bind the transmitter . However , the essentially vectorial nature of chemical synaptic transmission belies the possibility that the postsynaptic cell can influence synapse formation or transmitter release by the presynaptic cell . Studies of synapse development and regulation have shown that postsynaptic cells also play an active role in synapse formation . In the CNS , postsynaptic cells may also produce retrograde signaling molecules , such as nitric oxide , that diffuse back into the presynaptic terminal and modulate the strength of the synaptic connection . Furthermore , the presynaptic membrane at many synapses has receptors that may either inhibit or facilitate the release of transmitter .
Name and explain the basis by which ion channels can be distinguished .
Classes of ion channels: electrophysiology , pharmacological and physiological ligands , intracellular messengers , and sequence homology. Electrophysiology- ion selectivity, voltage dependence, and kinetics of gating Pharmacological and physiological ligands - sensitivity to toxins, agonist, ligand-gated channels Intracellular messengers - other ions or cGMP ( for example ) Sequence homology- amino acid sequencing, which gene encodes, 3D structures
Using the Electrochemical potential energy difference equation difference When X is uncharged , explain the condition where equilibrium occurs .
Equilibrium can occur only when [ X ] is equal on the two sides of the membrane
Using the Electrochemical potential energy difference equation When X is charged , but the voltage difference is zero , explain the condition where equilibrium occurs .
Equilibrium can occur only when [ X ] is equal on the two sides of the membrane .
When neither the chemical nor the electrical term is zero , explain the condition where equilibrium occurs .
Equilibrium can occur only when the two terms are equal but opposite sign .
Explain facilitation , potentiation , and depression . Also , describe how they may occur .
Facilitation is a short - lived enhancement of the postsynaptic potential in response to a brief increase in the frequency of nerve stimulation . One way facilitation may occur is by a transient increase in the mean number of quanta per nerve stimulus . Potentiation is a long - lived and pronounced increase in transmitter release that occurs after a long period of high - frequency nerve stimulation . This effect can last for minutes after the conditioning stimulus . Potentiation may be caused by a period of intense nerve firing , which increases [ Ca² + ] in the presynaptic terminal and thus increases the probability of exocytosis . Synaptic depression is a transient decrease in the efficiency of transmitter release - and , consequently , a reduction in the postsynaptic potential - in response to a period of frequent nerve stimulation . Depression may result from a temporary depletion of transmitter - loaded vesicles in the presynaptic terminal that is , a reduction in the number of available quanta .
millisecond time scale whereas metabotropic receptors mediate slow , biochemically mediated synaptic responses in the range of seconds to minutes .
G
When equilibrium is +125 mV and drive force is -180 mV calcium channels opened which net direction would the calcium flow ? Explain your answer .
If V. is more negative than Ex , then the membrane voltage is too negative for X to be in equilibrium . As a result , if X is positive , the cation will tend to passively enter the cell .
What feature of the capacitative current allows one to measure ionic conductance ?
If we clamp voltage, capacitative current flows for brief time at voltage transition and disappears by the time Vm reaches new steady value. After Ic has decayed to zero, any additional changes in Im must be due to changes in Ix.
The time course of sodium current in the presence of TEA is distinctly biphasic . Explain what is meant by biphasic and what is responsible for it .
Immediately after a depolarizing voltage step to a Vm of -30 mV , for example , the inward Is ( downward going ) reaches a " peak " value and then returns to zero . The initial phase of this time course ( before the peak ) is called activation , and the later phase ( after the peak ) is called inactivation .
Explain what miniature end - plate potentials ( also known as MEPPS or minis ) are and what they suggest happens at the presynaptic terminal ?
In 1950 , Fatt and Katz observed an interesting kind of electrophysiological " noise " in their continuous high - resolution recordings of Vm with a microelectrode inserted at the end - plate region of a frog muscle fiber . Their recordings from resting muscle fibers that were not subjected to nerve stimulation revealed the occurrence of tiny depolarizations of -0.4 mV that appeared at random intervals . These small depolarizations were blocked by the ACHR antagonist curare and they increased in size and duration with application of the AChE inhibitor neostigmine . Because the spontaneous Vm fluctuations also exhibited a time course similar to that of the normal EPP , they were named miniature end - plate potentials ( also known as MEPPS or minis ) . These observations suggested that even in the absence of nerve stimulation , there is a certain low
Explain threshold , absolute refractory period , and relative refractory period in terms of the HH model .
In addition to delineating the basis of the action potential waveform , the HH model also explains threshold behavior and the refractory period . The number of Na + channels activated by the stimulus is determined by the voltage dependence of the activation process ( i.e. , m parameter ) . Opposing the local depolarization that is produced by the current flowing through these Na + channels are current losses that occur because of passive spread of the current through intracellular and extracellular fluid . Also opposing depolarization is the hyperpolarizing effect of currents through any open K + or Cl - channels in the membrane . Thus , the threshold is the level of depolarization at which the depolarizing effect of the open Na channels becomes sufficiently self - reinforcing to overcome these opposing influences . Once threshold is reached , further activation of Na + channels rapidly drives Vm toward Exa . The basis of the absolute refractory period , the time during which a second action potential cannot occur under any circumstances , is Na + channel inactivation . In other words , it is impossible to recruit a sufficient number of Nat channels to generate a second spike unless previously activated Na + channels have recovered from inactivation ( i.e. , h parameter ) a process that takes several milliseconds . The relative refractory period , during which a stronger than normal stimulus is required to elicit a second action potential , depends largely on delayed K + channel opening ( i.e. , n parameter ) . In other words , for a certain period after the peak of the action potential , the increased K + conductance tends to hyperpolarize the membrane , so a stronger depolarizing stimulus is required to activate the population of Na + channels that in the meantime have recovered from inactivation .
Explain the two factors that can influence the open probability of BKca channels .
In patch - clamp experiments , all Kc channels are easily recognized because the open probability of individual channels increases with increasing [ Ca 2+] on the intracellular surface of the membrane patch . In addition , the Po of BKca increases with positive voltage .
Conclude why recording in curare treated muscle at various distances from the end plate , the amplitude of the potential change is successively diminished and its peak is increasingly delayed .
In this experiment , curare blockade allows only a small number of ACHR channels to open , so that the EPP does not reach the threshold to produce an action potential . If the experiment is repeated by inserting the microelectrode at various distances from the end plate , the amplitude of the potential change is successively diminished and its peak is increasingly delayed . This decrement with distance occurs because the EPP originates at the end - plate region and spreads away from this site according to the passive cable properties of the muscle fiber . Thus , the EPP is an example of a propagated graded response .
Explain two-electrode voltage clamping .
Involves impaling cell with two sharp electrodes - one for monitoring Vm - one for injecting the current feedback amplifier injects opposing current when voltage-sensing electrode detects difference from command voltage to maintain constant Vm magnitude of the current needed to keep Vm constant is equal, but opposite in sign to membrane current accurate measurement of the total membrane current ( Im ).
Explain how intracellular Mg2 + can cause inward rectification of the inward - rectifier potassium channel . What is responsible for the inward rectification in physiological conditions ?
Inward rectification is due to intracellular block of the channel by Mg2 + . Selective inhibition of outward K + current in the presence of intracellular Mg2 + results from voltage - dependent binding of this divalent metal ion . Positive internal voltage favors the binding of Mg2 + to the inner mouth of this channel , as would be expected if the Mg2 + binding site is located within the transmembrane electrical field . Because Mg2 + cannot permeate the channel , it acts as a blocker of outward K + current . However , negative values of Vm pull the Mg2 + out of the channel . Moreover , incoming K + tends to displace any remaining Mg2 + . Thus , the Kir channel favors K + influx over efflux . Under physiological conditions , intracellular cationic polvamines such as spermine and spermidine block outward movements through Kir channels in a fashion similar to Mg2 + and largely account for the Kir rectification .
Local anesthetics that are used clinically , such as procaine , lidocaine , and tetracaine are " use dependent . " Explain what " use dependent " means and why it occurs .
Local anesthetics that are used clinically , such as procaine , lidocaine , and tetracaine , reversibly block nerve impulse generation and propagation by inhibiting voltage - gated Na + channels . The action of these drugs is " use dependent , " which means that inhibition of Na + current progresses in a time - dependent manner with increasing repetitive stimulation or firing of action potentials . Use dependence occurs because the drug binds most effectively only after the Na + channel has already opened . This use - dependent action of the drug further enhances inhibition of nerve impulses at sites where repetitive firing of action potentials takes place .
Explain what the equation to the right represents . I = NPoi
Macroscopic ionic current (I ) number of channels ( N ) within the membrane area unitary current of single channels ( i ) probability of channel opening (Po)
Contrast reciprocal electrical synapses versus rectifying electrical synapses
Many types of gap junctions pass electrical current with equal efficiency in both directions , these are termed reciprocal synapses . In other words , the current passing through the gap junction is ohmic ; it varies linearly with the transiunctional voltage ( i.e. , the Vm difference between the two cells ) . However , the crayfish synapse described by Eurshnan and Potter allows depolarizing current to pass readily in only one direction , from the presynaptic cell to the postsynaptic cell . Such electrical synapses are called rectifying synapses to indicate that the underlying junctional conductance is voltage dependent .
Contrast the flow of an action potential initiated at one end of a nerve fiber versus at a central location on the nerve fiber . What feature of the action potential is responsible for this phenomenon ?
Nerve and muscle fibers conduct impulses in both directions if an inactive fiber is excited at a central location . However , if an action potential is initiated at one end of a nerve fiber , it will travel only to the opposite end and stop because the refractory period prevents backward movement of the impulse . Likewise , currents generated by subthreshold responses migrate equally in both directions .
units for resistance
Ohm
Draw the equivalent circuit model of a cell . With variable resistors , electromotive forces ( emfs ) , and capacitor .
Pic
total membrane current response from a sudden depolarization from -80 to - 20 mV recorded in a voltage - clamp experiment for the squid giant axon . Draw the same current following the blockade of potassium with TEA . Draw the same current following the blockade of sodium with TTX .
Pic
Explain the refractory period (both absolute and relative) and what they arise from .
Refractory period: a finite time elapsed after one AP fires, before it is possible to trigger a second impossible or more difficult to produce a second spike is the refractory period .The refractory period consists of two distinct phases . The initial phase , the absolute refractory period , lasts from initiation of the spike to a time after the peak when repolarization is almost complete . Throughout this first phase , a second action potential cannot be elicited , regardless of the stimulus strength or duration . During the second phase , the relative refractory period , the minimal stimulus necessary for activation is stronger or longer than predicted by the strength - duration curve for the first action potential . The two phases of the refractory period arise from the gating properties of particular Na + and K + channels and the overlapping time course of their currents .
Draw an equivalent - circuit model of an axon , labeling the passive cable properties ( rm , to . Li and cm ) . Also , name and define those passive cable properties .
Rr
single channel currents
Single channel currents are the smallest , nearly rectangular transitions of current correspond to the opening and closing of a single channel . When two or three channels in the patch are open simultaneously , the measured current level is an integral multiple of the single channel or " unitary " transition .
Explain the graded voltage changes that occur in hyperpolarizations and subthreshold depolarizations **
Smaller or subthreshold depolarizations do not elicit an action potential . Both hyperpolarizations and subthreshold depolarizations behave like graded
What are the original Hodgkin and Huxley equations for macroscopic sodium and potassium currents ?
The HH analysis provides a description of macroscopic currents for Na + ( a ) and K + ( IK ) , but relates these macroscopic currents not to single channel currents but to the maximal conductance of the membrane to Na + ( G ) or K + ( GK ) . Here , Vm is the membrane potential , Ek is the equilibrium potential for K + , and Exis the equilibrium potential for Nat . They found it necessary to use the fourth power of n to account for the sigmoid - shaped time dependence ( or lag phase ) for K + -current activation . Similarly , the m³ parameter is the probability of Na channel opening . In order to account for the inactivation phase of the Na + current , Hodgkin and Huxley proposed that the channel has a separate inactivation gate described by the parameter h .
Explain in detail how the S4 segment acts as the voltage sensor for voltage - gated channels
The S4 segment has four to seven arginine or lysine residues that occur at every third S4 residue in voltage - gated K + , Na + , and Ca2 + channels . The positively charged S4 segment acts as the voltage sensor for channel activation by moving outward when the membrane depolarizes . This movement causes the four S6 helices , which form the inner lining of the pore , to bend away from the pore axis , thereby opening the channel .
Explain the puzzling observations of early physiologists that acetylcholine activates skeletal muscle but inhibits heart muscle .
The acetylcholine response is mediated by two prototypic ACh receptors ( AChRs ) : ( 1 ) the Ach activated ion channel at the neuromuscular junction of skeletal muscle , an ionotropic receptor also known as the nicotinic AChR , and ( 2 ) the G protein - linked AChR at the atrial parasympathetic synapse of the heart , a metabotropic receptor also known as the muscarinic ACHR . The nicotinic versus muscarinic nomenclature is pharmacological based on whether the ACHR is activated by nicotine or muscarine , two natural products that behave like agonists . In the case of the ionotropic ( nicotinic ) receptor , opening of the ACHR channel results in a transient increase in permeability to Na + and K + , which directly produces a brief depolarization that activates the muscle fiber . In the case of the metabotropic ( muscarinic ) receptor , activation of the G protein - coupled receptor opens an inward - rectifier K + channel , or GIRK via By subunits released from an activated beterotrimeric G protein . 1 opening of GIRKS produces membrane hyperpolarization and leads to inhibition of cardiac excitation .
Hodgkin and Huxley defined a series of three dimensionless parameters , n , m , and h , each of which can have a value between 0 and 1. What do they each describe ?
The activation parameter n describes the probability that the K + channels are open . The activation parameter m describes the probability that the Na + channels are open . Because Hodgkin and Huxley observed that the Na + current inactivates , they introduced the inactivation parameter h to describe this process . The n parameter describes the probability that each of four " particles " in the K + channel is in the proper state for channel opening . It is believed that these four particles are the gates of the four K + channel subunits . The m parameter describes the probability that each of three particles in the Na + channel is in the proper state for channel opening . The h parameter describes the probability that an inactivation particle is not in the proper state for inactivating the Na + channel . Thus , a high h favors the open state of the channel .
What is the mechanistic cause of Myasthenia gravis ?
The cells of the thymus possess nicotinic AChRs , and the disease arises as a result of antibodies directed against these receptors . The antibodies then lead to skeletal muscle weakness caused in part by competitive antagonism of AChRs . Myasthenia gravis is now recognized to be an acquired autoimmune disorder in which the spontaneous production of anti - AChR antibodies results in progressive loss of muscle AChRs and degeneration of postiunctional folds .
Detail the channel - forming subunits of the inward - rectifier potassium channel family .
The channel - forming subunits of the inward - rectifier ( Kir ) K + channel family are relatively small proteins ( ~ 400 to 500 residues ) that do not contain the complete S1 to S6 core domain found in the Kv and Kca channel families . However , the Kir channels do have a conserved pore domain similar to the S5 - P - S6 segment of Kv channels . The conserved P region is the most basic structural element that is common to all K + channels . The absence of an S1 to S4 voltage sensing domain in Kir channels is consistent with their lack of steeply voltage - dependent activation
Explain how the transient voltage change that occurs during an action potential at a particular active site results in local current flow .
The cytosol of the active region , where the membrane is depolarized , has a slight excess of positive charge compared with the adjacent inactive regions of the cytosol , which have a slight excess of negative charge . This charge imbalance within the cytosol causes currents of ions to flow from the electrically excited region to adjacent regions of the cytoplasm . Because current always flows in a complete circuit along pathways of least resistance , the current spreads longitudinally from positive to negative regions along the cytoplasm , moves outward across membrane conductance pathways ( " leak channels " ) , and flows along the extracellular medium back to the site of origin , thereby closing the current loop . Because of this flow of current ( i.e. , positive charge ) , the region of membrane immediately adjacent to the active region becomes more depolarized , and Vm eventually reaches threshold . Thus , an action potential is generated in this adjacent region as well .
Explain how Tetnaus leads to a general increase in muscle tension and muscle rigidity .
The disease tetanus is caused by a neurotoxin ( tetanospasmin ) produced by Clostridium tetani The organism gains entry to its host via a cut or puncture wound . The toxin then travels along the peripheral nerves to the spinal cord , the major site of its attack . There , the toxin inhibits synaptic vesicle release by GABA and glycine interneurons which normally inhibit firing of the motor neurons that , in turn activate skeletal muscle Thus , because the toxin suppresses inhibition of the normal reflex arc , muscle contraction leads to profound spasms , most characteristically of the jaw muscles but potentially affecting any muscle in the body .
Explain what the P region of voltage - gated channels is and its function .
The extracellular linker region between the $ 5 and S6 segments is termed the P region ( for pore region ) and contains residues that form the binding sites for toxins and external blocking molecules such as TEA . The pore domain formed by S5 - P - S6 is the minimal structure required to form an ion - conducting pore for this class of channels . The P region also contains conserved
What does the molluscan peptide toxin ω-conotoxins , block and what effect does it have on the presynaptic terminal and neurotransmitter release ?
The molluscan peptide toxins called ω-conotoxins , block N - type Ca² + currents in a virtually irreversible fashion. Exposure of a frog nerve - muscle preparation to ω-conotoxin , thus inhibits the release of neurotransmitter.
Contrast the length constant versus the time constant
The parameter λ has units of distance and is referred to as the length constant or the space constant . One length constant away from the point of current injection , V is 1 / e , or -37 % of the maximum value of Vo . The significance of the length constant is that it determines how far the electrotonic spread of a local change in membrane potential can extend to influence neighboringregions of membrane . The longer the length constant , the farther down the axon a voltage change spreads . The membrane time constant ( Tm ) describes how rapidly Vm changes time at a particular site . Rather than determining the spread of voltage changes in space , as the length constant does , the time constant influences the spread of voltage changes in time and thus the velocity of signal propagation . The cable parameters of length constant and time constant determine the way in which graded potentials and action potentials propagate over space and time in biological tissue . These parameters are in turn a function of material properties that include resistance , capacitance , and geometric considerations
Explain in detail why the reversal potential for the nicotinic ACHR channel is close to 0 mV .
The reversal potential is near o mV because the nicotinic ACHR has a poor selectivity for Na versus K. When the nicotinic AChR channel at the muscle end plate opens , the normally high resting permeability of the muscle plasma membrane for K * relative to Na * falls so that Na * and K + become equally permeant and Vm shifts to a value between Ex ( approximately -80 mV ) and Ex ( approximately +50 mV ) .
How are Kv channels inactivated ?
The structural basis for one particular type of K + channel inactivation , known as N - type inactivation , is a stretch of -20 amino - acid residues at the N terminus of some fast - inactivating Kv channels . This domain acts like a ball to block or to plug the internal mouth of the channel after it opens ; the result is inactivation . Thus , this process is also known as the ball - and - chain mechanism of K + channel inactivation . Particular kinds of ß subunits that are physically associated with some isoforms of Kv channels have structural elements that mimic this N terminal ball domain and rapidly inactivate K + channel a subunits that lack their own inactivation ball domain . Many K + channels also exhibit a second , slower C - type inactivation which appears to involve a constriction of the outer mouth of the pore .
What enzyme is present in high concentrations at the basal lamina and what is its role in synaptic transmission ?
The synaptic basal lamina also contains a high concentration of the enzyme acetylcholinesterase ( AChE ) , which ultimately terminates synaptic transmission by rapidly hydrolyzing free Ach to choline and acetate .
Describe the time course of an action potential in terms of sodium and potassium conductances and their respective equilibrium potentials .
The time course of the action potential can be dissected into an initial , transient increase in Na + conductance ( and thus permeability ) , followed by a similar but delayed increase in K + conductance . As one predicts from the GHK voltage equation , a transient increase in Na + conductance shifts Vm toward the positive Na + equilibrium potential (Ena) . The subsequent
Explain what saltatory conduction is and how it works .
The unique anatomy of myelinated axons results in a mode of impulse propagation known as saltatory conduction . In myelinated peripheral nerves , the myelin sheath is interrupted at regular intervals , forming short ( ~ 1 - um ) uncovered regions called nodes of Ranvier . The length of the myelinated axon segments between adjacent unmyelinated nodes ranges from 0.2 to 2 mm . In mammalian axons , the density of voltage - gated Na + channels is very high at the nodal membrane , whereas K * channels are localized in the paranodal regions flanking each node . Current flow that is initiated at an excited node flows directly to adjacent nodes with little loss of transmembrane current through the internode region . In other words , the high membrane resistance in the internode region effectively forces the current to travel from node to node .
What are the different functional properties of junctional and nonjunctional AChRs and what is responsible for them ?
The unitary conductance of noniunctional receptors is smaller and the single - channel lifetime is longer in duration than that of junctional receptors . Measurements of currents at different voltages yielded single - channel current - voltage ( I - V ) curves showing that the channel formed with the e subunit had a unitary conductance of 59 picosiemens ( pS ) , whereas that formed with the y subunit had a conductance of 40 pS . The mean lifetime of single - channel openings at o mV was 1.6 ms for e - type and 4.4 ms for y - type receptors , which closely corresponds to values found in adult muscle and native fetal , respectively . The basis for this phenomenon is a difference in subunit composition . The noniunctional ( or fetal ) receptors are a pentameric complex with a subunit composition of a Byd in mammals , just as in the electric organ of the torpedo ray . For the junctional ACHR in adult skeletal muscle , substitution of an e subunit for the fetal y subunit results in a complex with the composition a Be8 .
Contrast the L - type versus the T - type Ca2+ channels .
These two types of Ca² + channel are named L - type ( for long - lived ) and T - type ( for transient ) channels . For L - type , if the cell - attached patch , initially clamped at -50 mV , is suddenly depolarized to +10 mV , currents appear from a large - conductance ( 18 to 25 pS ) , slowly inactivating Ca² + channel . For T - type , if the same patch is initially clamped at -70 mV and depolarized to only -20 mV , currents appear instead from a small - conductance ( 8 pS ) , rapidly inactivating Ca² + channel . L - type channels are activated at a higher voltage threshold ( more positive than -30 mV ) , mediate the long - lived plateau phase of slow action potentials and provide a more substantial influx of Ca² + for contractile and secretory responses . T - type channels are activated at a lower voltage threshold ( more negative than -30 mV ) than are other types of Ca² + channels and are also inactivated over a more negative voltage range . These characteristics of T - type channels permit them to function briefly in the initiation of action potentials and to play a role in the repetitive firing of cardiac cells and neurons .
Explain why after the addition of QX - 222 , an analog of the local anesthetic agent lidocaine , to the extracellular side , the channel exhibits a rapidly flickering behavior .
This flickering represents a series of brief interruptions of the open state by numerous closures . This type of flickering block is caused by rapid binding and unbinding of the anesthetic drug to a site in the mouth of the open channel . When the drug binds , it blocks the channel to the flow of ions . Conversely , when the drug dissociates , the channel becomes unblocked
The exquisite selectivity of Ca² + channels under physiological conditions endows them with special roles in cellular regulation . When activated by a depolarizing electrical stimulus or a signal - transduction cascade , these Ca² + channels mediate an influx of Ca² + that raises [ Ca² + ] i . Thus , in serving as a major gateway for Ca² + influx across the plasma membrane , Ca² + channels
U
Ohm's law and explain what each value represents
V = IR , V is voltage , I is current , and R is resistance
Compare and contrast dense - core secretory granules versus clear synaptic vesicles .
Vesicles destined to contain peptide neurotransmitters travel down the axon with the presynthesized peptides or peptide precursors already inside . On arrival at the nerve terminal , the vesicles - now called dense - core secretory granules ( 100 to 200 nm in diameter ) -become randomly distributed in the cytoplasm of the terminal . Vesicles destined to contain nonpeptide . neurotransmitters ( e.g. , ACh ) travel down the axon with no transmitter inside . On arrival at the nerve terminal , the vesicles take up the nonpeptide neurotransmitter , which is synthesized locally in the nerve terminal . These nonpeptide clear synaptic vesicles ( 40 to 50 nm in diameter ) then attach to the actin - based cytoskeletal network . At this point , the mature clear synaptic vesicles are functionally ready for Ca² + -dependent transmitter release and become docked at specific release sites in the active zones of the presynaptic membrane .
Detail the three roles of calcium channels mentioned in the text .
Voltage - gated Ca² + channels contribute to the depolarizing phase of action potentials in certain cell types . Notably , the gating of voltage - gated Ca² + channels is slower than that of Na + channels . Whereas Na + channels are most important in initiating action potentials and generating rapidly propagating spikes in axons , Ca² + channels often give rise to a more sustained depolarizing current , which is the basis for the long - lived action potentials in cardiac cells , smooth - muscle cells , secretory cells , and many types of neurons .
How can a steady state persist when X is not in equilibrium?
When some device (such as a mechanism for actively transporting X) compensates for the passive movement of X o prevent ICF and ECF [X] from changing with time combination of a pump and a leak maintains [X] and the passive flux of X
How are tetanus toxin and botulinum toxins potent inhibitors of neurotransmitter release ?
both toxin proteins have zinc-dependent endoproteinase activity . enter nerve terminals and specifically cleave three different SNARE proteins required for synaptic vesicle exocytosis
Explain the hydrophobic and hydrophilic domains of a channel protein .
channel proteins have several segments of hydrophobic amino acids long enough to span the lipid bilayer as an a helix. channel has N membrane spanning segments has N + 1 hydrophilic domains of variable length that connect or terminate the membrane spans
Describe the superfamily of voltage-gated channels .***
channels because their pore-forming subunit contains only one S1 through S6 domain Voltage gated K + channels are homotetramers or heterotetramers of monomer subunits . The pore forming subunits of Na + and Ca2 + channels both comprise four domains ( I II , III , and IV ) , each of which contains the S1 through S6 structural motif that is homologous to the basic voltage - gated K + channel subunit or monomer .
Label and describe the threshold , peak , afterhyperpolarization depolarizing phase , repolarizing phase , and overshoot of an action potential***
depolarizing stimulus causes Vm to become more positive than a threshold voltage - triggers an action potential initial depolarizing phase Repolarizing ( positive going ) phase of an action potential consists of a rapid and smooth Brief increase in Vm from the negative resting potential to a maximum positive value , peak , that typically lies between +10 and +40 mV . This sharp rise in V m to the peak voltage of the action potential is then followed by a slower repolarizing ( negative - going ) phase . The part of the action potential that lies above o mV is Hyperpolarizing called the overshoot . The repolarization phase phase may lead directly back to Yrest , or it may undershoot and give rise to a voltage minimum that is more negative than Vrest before relaxing back to Vrest . Such an undershoot is an example of an afterhyperpolarization .
outside-out recording
ends of membrane anneal & extracellular domain/surface accessible optimal for studying how channel activity is influenced by extracellular chemical signals, like neurotransmitters
inside-out recording
exposed to air & cytoplasm (intracellular) domain/surface is accessible allowance to change the medium to which the intracellular surface of the membrane is exposed particularly valuable when studying the influence of intracellular molecules on ion channel function
Explain inward current , outward current , and the role a reversal potential has on both .
inward current- current of ions flowing into the cell. defined in electrophysiology as negative. outward currents- current flowing out of the cell. defined as a positive current. The reversal potential ( Vrev) is precisely the voltage that the direction of current reverses
Cell-attached voltage clamp
mild suction & tight contact between pipette and membrane no ions can flow between the pipette and the membrane. measures the current through a single ion channel. allows experimental control of the membrane potential to characterize the voltage dependance of membrane currents
probability of transmitter release at the presynaptic terminal , resulting in the opening of a small number of AChRs in the postsynaptic membrane .
probability
What are gap junctions ?
protein channels that connect two cells via a large, unselective pore diameter of >1.4 nm allows solutes as large as 1 kDa to pass between cells (Ca² +, glucose, cyclic nucleotides, IP3, ADP, ATP) provide pathways for chemical communication and electrical coupling between cells
Define Rheobase and Chronaxie
rheobase is minimum intensity of stimulation required to generate an action potential when the stimulation is of infinite duration . When stimulus intensity is twice the rheobase , the minimum duration required to achieve an action potential is the chronaxie
whole-cell recording
strong pulse of suction & cytoplasm is continuous with pipette interior allows measurements of electrical potentials and currents from the entire cell allows diffusional exchange between solutions in the pipette and cytoplasm
Conclude what the GHK voltage equation tells us .
zero net current flow is the steady - state condition that exists for the cellular resting potential Vm = Vrev logarithmic term indicates resting Vm depends on conc . gradients and ion permeabilities resting Vm depends primarily on the concentrations of the most permeant ion .
