EXAM3: Membrane potential and synapse
0.5-2
1 synapse( excitatory or inhibitory) changes the post synaptic potential by ____mV
mho
1__=1siemen
postsynaptic,presynpatic
2 Types of Inibition: 1. Inhibitory NT's bind to receptors on ____ membrane. 2.Inhibitory NT's bind to receptors on other _____ excitatory terminals.
Temporal,Spatial
2 Types of summation
ionotrophic,metabotropic
2 general types of neurotransmitter receptors:
Nicotinic, Muscarinic
2 types of ACh receptors:
g
?=Amps/Volts=mho
dendrite,neuronal, presynaptic
A presynaptic terminal can be on a ___, ___ cell body or another ____ terminal.
catecholamines
A subclass of amines is ____.
Acetly-CoA,Choline,presynaptic
ACh is made in presynaptic terminal by combining ____ & ____. Choline acetlytransferase effects this synthesis. After acetlycholinesterase breaks down the ACh in the synaptic cleft, the choline is transported back to ____ terminal for re-use.
spinal cord,cholinergic
Acetlycholine (ACh)- all motor axons arising from ____ i.e. neuromusclar junction. ACh is also found in the autonomic nervous system. It is used in neocortex & is thought to play a role in memory function. One of the pathologies of Alzheimer's disease is the loss of ____ neurons.
saltatory
Action potential appears to jump from one node to next, the process is called _____ conduction.
Depolarization
An action potential can be generated only if a critical number of Na+ channels are recruited. Voltage sensitive Na+ channels open up in a range of membrane potential (-70 to +40mV).
inactivation,repolarizing
An important characteristic of the Na+ channel inactivation process is that the _____ gate will not re-open until the membrane potential returns either to or nearly to the original resting membrane potential level. Therefore it is not possible for the Na+ channels to open again without the nerve fiber first ______.
SSRI's
Antidepressants such as ______ (selective serotonin re-uptake inhibitors) inhibit the reuptake up 5-HT @ teh synpatic cleft thereby elevating the level of 5-HT. Some think that clinical depression may in some classes be linked to too little 5-HT release in the serotonergic presynaptic terminals.
resting membrane,
Because of electrogenic nature of the Na+/K+ ATPase, it makes a contribution to the _____ potential to cells.
novocain
Blocking the voltage sensitive Na+ channels is the mechanism of local anesthetics i.e. procaine ( _____) or tetracaine.
5x10-5,1.2
Ca2+ cont. inside___mM & outside ___mM
K+,Na+
Cell membranes are not equally permeable to all ions. Na+/K+ cross the cell membrane via Na+/K+ "leak channels". These leak channels are far more permeable to __ than ___.
extracellular
Cells in tissue exist in osmotic equilibrium because, by definition, the total number of intracellular particles per unit volume equals the total number of particles in the _____ fluid.
Na+,K+
Changes in Na+/K+ conductances ( permeability) during the course of the action potential: ____ condectance increases several thousandfold during the early stages of the AP, whereas ___condutance increases only about 30-fold during the latter stages of the AP & for a short period thereafter.
4,103
Cl- cont. inside ___mM & outside ___mM
dopamine
Cocaine and nicotine both elevate the level of ___ in the brain. Elevated dopamine in the brain is a major factor in additive behavior.
SSRI's
Common_____ are Prozac, Paxil & Zoloft
electrochemical potential
Concentration gradient and electrical potential acting together is called
alpha
Curare is an ____ toxin from plants. Used as poison tips of darts & spears in South America.
explode
Donnan equilibrium does not exist in real biological systems because the cell will ____, not accounting for movement of water( osmotic pressure of water not taken into account.
personality,Chlorpromazine
Dopamine in the brain plays a key role in ____. Hyperactive dopaminergic neurons may be involved in some form of psychosis. ____, a common drug used with spychotic patients is an inhibitor of dompaminergic neurons.
Valium,Xanax,Halcion, barbiturates
Drugs that work as agonists for GABA receptors benzodiazepines like ____ (3) and all _____
500-5000
During the activation state of Na+ channel, Na+ ions can pour through the channel, increasing the Na+ permeability of the membrane as much as ____ fold.
hydrolyzed
EPP are transient because the AcH is quickly ____
Nernst potential
Eion stands for
concentration gradient,electrical gradient
Electrochemical equilibruim occurs when elctrochemical potential is zero, in other words when ______=______ with opposing directions
V,Nernst
Em-Eion is used in place of ___(electrical potential in volts).The actual flow of ions, current (amps) is contingent upon how far away the cell membrane potential is from a given ion's ____ potential.
K+,Na+,Na+,K+
Even though the membrane is much more permeable to ___ compared to ____, more ___ will enter the cell than ____because of the Nernst equation.
norepinephrine,epinephrine,dopamine
Examples of catacholamines:(3)
Cl-
GABA and Glycine open ___ channels, which inhibits EPSP's
Nodes of Ranvier
Gaps that occur in the myelin sheath every 1 to 2mm. They are about 1 micrometer wide.
Amino Acid Transmitters
Glycine,Glutamate, are both
g=1/R
How is g ( conductance or permeability related to resistance)?
...
How much Na+ crosses an axon during action potential? In the range of 10^-12 at a given point (pmole). Therefore the change in ion concentration inside vs. outside the cell is not measurable with current instrumentation. In fact, each sequential action potential is not dependent upon the extrusion of Na+ by the Na+/K+ ATPase pump because there is ample Na+ concentration gradient to drive the depolarization of the membrane thousands of time with no pumping of the Na+/K+ ATPase.
zero
If Em is -90mV & the Nernst value for K+ is -90mV the actual flow of K+ across the membrane is ____, regardless of the conductance value.
Nernst equation
If concentration gradient is known for an ion, u can calculate the equilibrium potential for the ion via ______
equal
If equilibrium is achieved, then the Nernst values for each ion should be _____.
swelling,potential
If the Na+/K+ ATPase pump were the ONLY ion pump in a cell, then poisoning these pumps would lead to the cell ____ to the point of bursting because of the influx of Na+. But a normal cell has many different types of ion pumps that affect resting membrane ____.
pumps
If the cell were in Donnan equilibrium, the Nernst equation for each ion should yield the same measured membrane potential value. Of course it is not because of the presence of ____.
5,65
If you administer ouabain to a cell, the membrane potential will decrease about ___mV, ie membrane potential will shift from -70mV to -___mV. In some cells, this pump contributes upto 20mV.
proteins,Ion
In biological systems there are 2 factors that cause a potential across a membrane: 1. Higher concentration of charged ____ inside the cell than outside the cell. The cell membrane is impermeable to these proteins. 2.____ pumps that cause a net change in potential across the membrane
Em-Eion
In place of V we substitute _____ for Ohm Law
spatial,temporal,excitatory,inhibitory
In real life situations, ur neurons are a mix of ______&____ summations of both ____ & ____ synpatic input. Simultaneous summation of inhibitory & Excitatory Postsynpatic potentials
one
Inhibition: you can also have presynpatic inhibitory input in other inhibitory presynaptic terminals. Thus, ____ inhibitory neuron can inhibit another inhibitory neurons.
-90mV
Initially much more Na+ will rush in when AcH binds to the nicotinic receptor. All yyou need to do is get the postsynaptic membrane to threshold. Normal resting membrane potential or muscle is about _____
Na+,resting membrane
Its important to note that the ____ channel will not open its inactivation gate again after the AP has gone through, UNTIL the nerve fiber repolarizes and returns to the original __________ potential level.
140,4
K+ cont. inside___mM & outside ___mM
37
Length Constant: the distance over which the potential change decreases to ___% of its maximum value.
5
Length Constant:The maximum value is the difference between the highest and lowest potential recordings. Typically its 1-3mm in mammalian nerves or muscle. By ____mmm there is no measurable change.
myelin,schwann,oligodendrocytes
Many axons are insulated with ____, which is produced by _____cells in the peripheral nervous system & _______ in the central nervous system.
Histamine
NT in the hypothalamus. Functions are unknown
acetylcholine (ACh)
NT used as the neuromuscular junction is _______.
1/3
Na+ channels are open for ____ (fraction) of millisecond during AP.
10,142
Na+ cont inside __mM and outside ____mM
electrical
Nernst equation gives ___ potential needed to balance a given ionic concentration gradient across a membrane so that the net flux =0.
-86mV
Nernst value for K+
60mV
Nernst value for Na+
acetylcholinesterase
Nerve gas inactivates ____, causes muscle paralysis/
not
Nonopiod neuropeptides: most neuropeptides are_____ opiods
Facilitation
Often the summated postsynatpic potential is excitatory in nature, but has not risen high enough to reach the threshold for excitation. But the membrane is nearer to teh threshold for firing so that just a few more excitatory synapses can induce an AP.
L-Dopa
On pharmacolical strategy for Parkinson's Disease patients is to give patients ____. This elevates the level of dopamine in brain. It only works temporarily.
Miniature endplate potential (MEPP's)
One quantum (ACh in one vesicle) causes 1 MEPP. This will induce about a 1/2 mV change in postsynaptic membrane.
action potential, depolarize
One synapse does not cause an ____ in the next neuron. It takes many excitatory synapses to cause an AP ( in the downstream neuron). The nearly simultaneous arrival of presynaptic action potentials from several input neurons is necessary to_____ the post synaptic cell to threshold.
NT,V
Presynaptic Facilitation of Inhibition: In addition to presynaptic terminal being able to effect a more potent post-synaptic depolarization by temporal summation, rapid firing, the synapse can be potentiated by altering the amt of NT released. This can be done by altering the amount of Ca2+ influx u have at the presynatpic terminal, the more Ca2+ there is, the more ___ is released. Like wise w/inhibition. If you retard the amt of Ca2+ influx, u will reduce the amt of ____ released.
Ouabain
Probably if you poisoned the Na+/K+ pumps with ____ then Na+ would leak in and water would follow causing the cell to rupture.
Substantia Nigra
Region fo the brain with highest number of dopaminergic neurons
Chemical Synapse
Release of a transmitter substance i.e. neurotransmitter ( NT) from the presynpatic neuron. NT's bind to a receptor on the postsynaptic terminal or motor endplate (muscle)
K+
Repolarization: is caused by voltage sensitive ____channels(different channels from K+/Na+ channels).
-90,slowly
Repolarization: the voltage sensitive K+ channels begin to open up as the membrane potential rises above ___mV. The voltage sensitive K+ channels open up more ____ than the activation gates of the Na+ channels. repolarization occurs within a few msec.
Faraday's,310
Reworking the equation converting it from natural log to 10 base log & including ______ constant, molecular gas constant & assuming physiological temp of ____K ( 37o C) the (nernst/electrochemical potential) equation can be simplified to E=-61/z x log(inside/outside)
Spatial summation
Same principle as temporal summation, but instead of rapid repeated firing of an individual presynaptic terminal, there are multiple synaptic afferent fibers firing at close to the same time.
5-hydroxytryptoamine
Serotonin ( ______) asak 5-HT plays role in temperature regulation, which is controlled by hypothalamus, sleep on set, and mood.
Metabotropic
Serotonin, GABA, substance P as well as other NT have ____ receptors
Na+,K+
Since ___ leaks into the cell and ___ leaks out of the cell continuously, the Na/K+ ATPase pump counters this leakage by pumping Na+ out & K+ into the cell.
myelinated
Since ion flow is only at the nodes, much less Na+ conductance is needed to effect an action potential, by a factor of about 1000. Therefore, _____ axons are more metabolically efficient because fewer Na+'s have to be pumped back out by Na+/K+ ATPase pumps.
g
Since membrane is not equally permeable to all ions, we can give a weighted figure for each ion conductance. In other words, we can factor in a "__" value for each ion.
conductance,K+
Since normal resting cell membranes are 10-100x more permeable (which usually means _____ is greater) to K+ than Na+,___ concentration gradient is the most influential factor in the resting membrane potential.
Inhibitory
Some synapses are excitatory, some inhibitory. ___ synapses hyperpolarize the post synaptic cell membrane making it harder to depolarize.
muscle
Synaptic Troughs are on ___cell.
T
T or F conductance is aka permeability...
T
T or F: Goldman Eq is similar to Chord conductance eq
K+,leaky
TEA would change the voltage profile of an action potential; it would take more time for the membrane potential to go back down to resting because now you've lost the ability of the voltage sensitive ___ channels so only the _____ K+ channels are working to bring the potential back down.
NT,rapid
Temporal summation: Each time a terminal fires, the released ___ opens membrane channels for a msec of so. Because the postsynaptic potential lasts up to 15msec, a second opening of the same channels can increase the postsynaptic potential to a still greater level. Therefore, more ____ the rate of terminal stimulation, the greater the effect on postsynaptic terminal
slow,rapid
That is, the conformational change that flips the inactivation gate to the closed state is a ____ process, whereas the conformation change that opens the activation gate is a ____ process. Therefore, after Na+ channel has remained open for a few 10,000th of a second, it closes & Na+ ions can no longer pour to the inside of the cell.
concentration gradient,electrical potential
The 2 forces acting on ions ( or any charged molecule) in solution crossing a permeable membrane
Na+,K+
The ACh is the "ligand". When ACh binds to the receptor, the receptor changes configuration allowing____ to rush in & ___ to rush out, depolarizing the muscle membrane in the trough region.
electrogenic
The Na+/K+ is ____: it pumps out a net +1 w/each cycle, therefore it contributes to the resting membrane potential.
equilibrium
The Nernst equation is the ______ equation for a charged solute.
inside,outside
The Nernst equation will give the electrical potential of the _____ of the cell relative to the ____ of the cell.
Na+/K+ ATPase
The ____ pump plays a crtical role in osmotic equilibruim as it pumps out 3 Na+ for every 2 K+ in, with a net gain of 1 ion pumped out of the cell for each ATP hydrolysed.
3/2
The ___ratio of the Na+ out and K+ in ( Na+/K+ ATPase pump) simply maintains normal ion concentration gradients.
diameter,
The greater the ____of the axon, the greater the conduction velocity.
Ca2+,presnyaptic
The mechanism for synaptic release of NT from vesicles: Ap travels down axon & change in membrane potential @ presynaptic terminal opens up voltage sensitive ___channels. This influx of Ca2+ activates proteins in _____ terminal to move the NT vesicles to synaptic membrane where they fuse with it releasing their NT's.
depolarized,contraction
The mechanism for synaptic release of NT from vesicles: When postsynaptic membrane (muscle) is ______ enough to bring the membrane potential in the areas adjacent to the motor endplate to threshold, an AP is initiated across the surface of muscle & ______ occurs.
permeable,
The more ____ the membrane to a particular ion, the greater strength that ion will have in forcing membrane potential toward its equilibrium potential.
Long Term Potentiation (LTP)
The pre & postsynaptic terminal change such that more NT is released from presynaptic terminal per AP and/or postsynaptic terminal become more sensitive to excitatory NT. ___ can last from hrs to days to weeks. It is thought the ___ plays a role in memory.
-70,-90
The resting membrane potential ( ___to ___mV) is no where near the Nernst value to Na+ ( usually +58mV) Therefore, you have a large electrochemical gradient driving the sodium into the cell.
K+,K+
The resting membrane potential is near the Nernst value for ___, so less ___ crosses the membrane relative to Na+ even though the membrane is far more permeable to K+.
activation
The same increase in voltage that opens the activation gate also closes the inactivation gate. The inactivation gate, however, closes a few 10,000ths of a second after the _____ gate opens.
10^7
There are about ____ ACh receptors per endplate.
junctional folds
There are no ACh receptors in the ______. Voltage sensitive ion channels are present there.
permeability
There is no factor in the Nernst Eq. for ____ of charged particles relative to the membrane. ____ is irrelevant because we are talking about an equilibrium state. ___ will only affect the time it takes to reach equilibrium.
gradients
This Na+/K+ ATPase pumpe plays a major role in the creation and maintenance of the Na+/K+ ___ across the cell membrane.
Ca2+.NT,postsynaptic
Time course of 4 events related to synpatic transmission. An AP in presynaptic cell causes 1. presynatpic ___ channels to open and a Ca2+ current 2. to flow into the terminal leading to release of ___ from terminal. ( Ca2+ current is turned on late during falling phase of presynaptic AP). Postsynaptic response to transmitter beings soon afterward 3. & if sufficiently large, will trigger an AP in ____cell.4.
ACh
Toxin relapsed from bacterium Clostridum Botulinum block release of ___ causing paralysis. Botulism ( leathal food poisoning). Botox use in cosmotic injections to alleviate wrinkles.
Nicotinic Receptor
Type of ACh receptor found in motor endplate of a muscle cell. This is an ionotropic receptor that allows Na+ through upon binding w/ACh
Muscarinic Receptor
Type of ACh receptor found in other tissue such as smooth muscle. When ACh binds to it, changes occur inside the cell via G-proteins that results in closing of certain K+ channels. This of course alters the nature of membrane depolarization when NT's bind to ionotropic receptors on the same cell.
tyrosine-hydroxylase,decarboxylase,beta-hydroxylase
Tyrosine--> L-Dope-->Dopamie-->norepinephrine. ( name 3 enzymes above arrow)
mohs
Units of conductance (g)
Ohms
Units of resistance (R)
Ohm's Law
V=IR or I=V/R is whose law
Myelin
Very little ion movement occurs in regions of the axon that are wrapped with ____. ____ greatly increases the conduction velocity because of greater length constant. This is because there is no charge loss through the ____.
junctional, nicotinic
When Acetlycholine is released from the presynaptic terminal, ACh crosses the _____ cleft & binds to _____ ACh receptors in the cell membrane of the muscle cell.
Nernst
When a number of ions are distributed across a membrane & are removed from electrochemical equilibrium, each ion will tend to force the transmembrane potential towards its own equilibrium potential, as calculated from the _____ equation.
threshold
When the cell is depolarized to ______, it fires an action potential.
activation
When the membrane potential becomes less negative than during the resting state, rising from -90mV toward between -70 & -50mV, that causes a sudden conformational change in the activation gate, flipping it to an "open" open position. This is called the _____state.
activate,inactivate,K+
When the membrane potential is suddenly increased from the normal resting value of -90mV to a positive value of +10 mV for 2 milliseconds: Na+ channels open (____) & then close (____) before the end of the 2 milliseconds, whereas the ____channels only open (activate) & the rate of opening is much slower than for the Na+ channels.
all,none
When the stimulus is larger than threshold, the size & shape of AP does not change. As far as action potentials go, its ___ or ____.
does not change
When the stimulus is larger than threshold, the size & shape of AP does or does not change?
General Anesthetics
___ are usually GABA agonist
Morphine
___ is an opiate that is a poerful analgesic ( pain inhibition)
norepinephrine
___ is primary NT for postganglionic sympathetic neurons
peptides
____ are made up of 2-40 aa
Nitric Oxide
____ can be an inhibitory or excitatory NT, found in GI smooth muscles & CNS. Not in synaptic vesicles & is not released by exocytosis. This gas is membrane permeable.
Ouabain
____ is compound that selectively inhibits the Na+/K+ ATPase pump. It's used in experimentation to investigate the function of that pump.
Glutamate
____ is the most common excitatory NT
Tetradotoxin (TTX)
____ is used to selectivly block voltage sensitive Na+ channels. It is found in the ovaries, liver testes & eggs of the Pufferfish.
Substantia Nigra
____ plays a critical role in movement. These neurons die in Parkinson's Disease.
alpha,paralyses
____ toxins such as cobra venom binds to ACh receptors but does not open the ion channel. This _____ muscle ( diaphragm)
Threshold
_____ is achieved only when enough channels are open at the same time.
Tetraethylammonium (TEA)
_____ selectively block voltage sensitive K+ channels.
Gibbs-Donnan
______ equilibrium occurs when, across a charged membrane, there is no net change in ion distribution. The membrane potential is at the Nernst value for all ions.
NO synthase ( NOS)
_______ catalysis the production of NO by oxidizing arginine. In other words it removes an NO from that aa. ____ is stimulated by elevation of Ca2+ levels in presynaptic terminal
Acetylcholinesterase
_____breaks down ACh to acetate and choline. This enzyme is found on teh external surface of the post-junctional membrane.
Excitatory Post synaptic potential ( EPSP)
a transient depolarization of the postynaptic neuron evoked by action potential(s) of presynaptic neurons(s). Opens Na+ channels fro about 1-2msec. The decrease in membrane potential(depolarization) dies away over about 15msec. (graded, does not reach threshold)
Inhibitory Post Synpatic Potential ( IPSP)
a transient hyperpolarization elecitited by action potentials of the presynpatic neurons(s). Opens ion (K+ or Cl-) channels for about 1-2 msec. The increase in membrane potential (hyperpolarization) dies away over about 15msec.
Vasoactive Intestinal Polypeptide ( VIP)
acts as an inhibitory NT in smooth muscle
Threshold
amount of depolarization that is required to open enough voltage sensitive Na+ channels which leads to the initiation of an action potential.
Multiple Sclerosis
an autoimmune disease where the body attacks the myelin on axons. When the myelin is stripped away those axons cannot carry an action potential.
Myasthenia Gravis
autoimmue disease where antibodies attack ACh receptors.
Adrenal Medulla,epinephrine
cells of ____ add methyl group to norepinephrine to make ____ ( aka adrenaline)
Opiates
drugs that derive from opium poppy liek heroin. Acts on opiod receptors as an agonist
Accommodation,inability
during slow depolarization, voltage sensitive Na+ channels are activated & deactivated without the membrane reaching threshold. This results in the _____of the membrane to have an action potential regardless of the stimulus.
Opiods
endogenous opioid peptides like enkephalins, endorphins, dynorphins
Substance P
found in CNS, Gi tract & DRG ( dorsal root ganglion). It is involved in pain transmissions, smooth muscle contraction
decarboxylase
glutamate--GABA via which enzyme?
Glycine
inhibitory NT, found in neurons of spinal cord ( AA transmitter)
gamma-aminobutryric acid ( GABA), GABAergic
inhibitoryNT, most common NT in the CNS. It is estimated that 1/2 of all synapses are ____
Neuromuscular junction
motor neurons synapse at the skeletal muscle
Glutamate, Asparatate
name 2 excitatory amino acids ( EAA's)
Amines
norepinephrine, epinephrine, domapine, serotonin & histamine make us what class of NT's?
Divergence
one axon to multiple neurons
convergence
one neuron receives multiple inputs from many neurons.
Absolute Refractory Period
period following an action potential when another action potential cannot be initiated because the Na+ channels will not open.
Relative Refractory Period
period following an action potential when the cell membrane potential is hypolarized & a larger stimulus is required to initiate a new action potential.
Endplate potential (EPP)
the depolarization of motor endplates because of ACh binding to receptors. One EPP will be sufficient to induce and AP in muscle because of the large size of motor end plate & significant amt of ACh released as a result of an AP in presynpatic membrane.
Donnan effect
the movement of ions in & out of a cell because of greater concentration of charged protein inside the cell relative to the outside.
Propagation
the sequential generations of new action potentials down a nerve fiber. Because the size & shape of the action potential usually does not change, only the variation in frequency of the action potentials can be used to "code" for information transmission along axons. The maximum frequency is limited by the duration of the absolute refractory period (1 msec) to about 1000 impulses per second in large mammalian cells.
Conduction velocity
the speed at which an action potential is propagated down an axon.
Ionotropic receptors
these are recptors that are aslo ion channels. When a ligand ( NT) binds to it, the channel opens up and ions flow through
Metabotropic receptors
these receptors are not ion channels. When a ligand(NT) binds to it, it causes a change in the cell by way of a 2nd msnger system
Inhibition
usually invovles the opening of Cl- channels by Nt's such as GABA, therefore hyperpolatizing the post synaptic membrane.
Hyperpolarization
voltage sensitive K+ channels are slow to close after repolarization, therefore the membrane potential becomes more negative than the resting potential.