Membrane Potential, Action Potential, The synapse
Calcium equilibrium potential
+ 107 mV
What happens without a functional Na+/K+ pump?
, the ion fluxes of the steady state would eventually accumulate, and the concentration gradients would disappear. Over time the cell would intracellular Na+ would increase, and the cell would become depolarized. With the pump disabled, the ions redistribute themselves until they are all in an equilibrium state. The negatively-charged anions trapped inside the cell attract cations in an effort to reach true equilibrium. This process eventually leads to cell swelling and lysis
what are some similarities with the action potential in different cell types?
- they all have a very rapid depolarization phase that is all or nothing it either occurs fully or not at all amplitude of action potential is independent of the amount of current that is produced (Larger stimuli does not create larger action potential
non-excitable cells have a resting membrane potential that range from
-5 mV to -15 mV
excitable cells have a resting membrane potential between
-50--85 mV
neuronal action potential importance
-Electrical component of "electrochemical" transmission in the central and peripheral nervous systems -Critical for neural integration of information coming from multiple sensory modalities -Allows for rapid and efficient signal transmission even over long distances
what are the for major ion channels present in the cell membrane that regulate membrane potential?
-ligand- gated -mechanically gated -always open(leak channels, play major role in resting membrane potential) -voltage-gated
Action potential conduction velocity can vary from __ to __ The main factors the determine this velocity are ___ and__
0.2 m/sec to 120 m/sec axon diameter and myelination wider diameter faster, more myelination faster
conductor
A device designed to transmit electricity, heat, etc.
Resistance
A material's opposition to the flow of electric current.
resting membrane potential
An electrical potential established across the plasma membrane of all cells by the Na+/K+ ATPase and the K+ leak channels. IN most cells, the resting membrane potential is approximately -70 mV with respect to the outside of the cell. describes electric potential difference of a cell at rest
the lipid bilayer acts as a
Capacitor plate, all capacitors have two electrical conductors separated by an insulator -they are able to store charge between these plates in an electric feild
Cl- equilibrium potential
Cl- would go into the cell and polarize the membrane to -83 mV
driving force
Driving Force in Cell with resting membrane potential of -60 Pottasium :-60 - -84 = 24 Sodium: -60 - 63 = -123 Chloride: -60- -83 = 23 Calcium: -60 - 107 = -167
the Nernst equation
Eion= (RT/zF) *(ln( ion outside./ion inside)) R= universal gas constant (8.381X 10-23 J/K) T= temperature (in Kelvins) oft constant assumed 293 Z= ion charge (valence) F= Faraday's constant (9.648x104 C/mol; electric charge
once the voltage-gated Na+ channels are closed,__________ within the K voltage gated channels.
repolarization occurs quickly. the slow closure of these voltage-gated potassium channels results in the hyperpolarization that occurs during the action potential
R in the cell is
resistance due tot he presence of a plasma membrane in ohms
Increasing the axons diameter affects velocity by decreasing axoplasm
resistance to ion flow easier to move things when tube is wider
While Ca2+ plays very little role in resting membrane potential due to the absence of Ca2+ leak channels, it has a critical role in, which can
role in intracellular signaling, which can then alter membrane permeability to other ions, ultimately influencing the membrane potential of the cell.
ion channels are characterized not only by how / what opens them but their
selectivity to specific ions
graded potential are changes in
shifts of current (I) amplitude- ie they are the result of a change in the flow ions across the membrane due to an alteration in conductance- such changes alter membrane potential
graded potentials are considered__ what numerical value difference is assigned?
small fluctuation any change less than 20 mV in membrane potential
___ will try to move the membrane potential toward its positive equilibrium potential, while___ will try to move the membrane potential toward its negative equilibrium potential
sodium, potassium
EK is the voltage required for diffusional and electrical forces to be equal and opposite. When not considering the influence of permeability, Eion is moderately influenced by , but considerably influenced
temperature but considerably influenced by intra- and extracellular ion concentrations.
phase 3 an of action potential initiation
the K+ is trying to reach its Ek+, and the cell* is becoming more negative than the resting potential, but before it can the voltage gated pottasium channels CLOSE and The activity of leak channels and hte NA/K pump restore the resting membrane potential
Capacitance
the ability of a conductor to store energy in the form of electrically separated charges
When depolarization of the membrane at the axon hillock reaches the threshold for that neural* cell, what happens
the abundant Na+ channels at the axon hillock (and initial segment) open and an action potential is initiated
In non-myelinated axons, the action potential must
the action potential must propagate continuously along the plasma membrane
the wave of depolarization of the AP in the neuron move from the cell body toward
the axon terminal. the forward regions the axolemma (axonal membrane) depolarize due the opening of Na channels
how is a voltage gated Na+ channel closed?
the conformational change induced by depolarization also closes the inactivation gate but this process is delayed (very brief delay~ .1ms) so it is said to be time dependent now far less permeable to Na+ membrane potential begins to return to resting potential. the inactivation gate will not open again until the membrane returns to resting potential even if there is a depolarizing event, no Na+ can enter the cell until the inactivation gate opens- This is what results in the absolute refractory period
conductance (G)
the ease with which ions flow through a channel G = 1/R it is simply the reciprocal of resistance for our purposes it is how easily an ion can move through an ION channel in a membrane
a cells resting membrane potential is based on
the equilibrium potential of multiple ions as well as on membrane permeability
I in the cell is
the flow of charged particles through "conductors" in the membrane ( in amperes)
the amplitude of the graded potential is dependent on
the intensity of the stimulus
The distance between nodes and the number of voltage-gated Na+ channels at the node influence
the speed of conductance
if there is a LARGE difference between equilibrium potential and resting membrane potential then
there is a large electrochemical gradient ( driving force) for that ion
on myelinated axons, as the depolarization wave moves down the axon it activates what
these voltage-gated Na+ channel in the nodes of Ranvier and propagates (or re-amplifies) the signal
what is the role of pumps and active transport in membrane potential
they are needed to offset the continuous leakage of ions across membrane important for working against both concentration gradients and electrical forces
the presence of inhibitory potentials in neurons result in what
they hyperpolarize the membrane, which also serve to diminish membrane depolarization
the repolarization from the K channels in the axolemma of a neuron is important because
this repolarization prevents the action potential from moving backwards (back propagation). For this reason we say that the movement of the action potential is unidirectional
the myelin sheath is composed of __ which provide
tightly wrapped lipid bilayers and specialized proteins insulation which decreases the decay of the depolarizing wave and support to axons
what closes the voltage-gated potassium channel?
until the Na+ channel closes both gated Na and K channels are open •Remember that Na+ has a stronger driving force, so with increased permeability it is winning the tug of war
when an excitatory potential depolarizes a neurons membrane this depolarization
will travel towards the axon hillock (which possesses a much higher density of voltage-gated Na+ channels then the cell body) diminishing exponentially with TIME and DISTANCE
Goldman-Hodgkin-Katz equation
•Includes the intra- and extracellular concentration of the three major ions influencing resting membrane potential •Includes permeability of the membrane to individual ions (both the number of ion channels and their permeability) •Also includes the other "constant" values discussed in the Nernst equation.
One critical function of myelin is to
•to increase the speed of electrical transmission (i.e. conduction velocity); the more myelin, the faster the conduction
it is the _______ that is correlated with the intensity of a stimulus and transmit variation in the information being transmitted
FREQUENCY of action potential
Nodes of Ranvier
Gaps in the myelin sheath to which voltage-gated sodium channels are cluster in the unmyelinated axolemma
initiation of an action potential in NEURONS
Incoming stimuli produces local changes membrane potentials (graded potentials). these Graded potentials can either be excitatory or inhibitory
sodium equilibrium potential
Na+: positive equilibrium -Driven inside by concentration, but once interior is too positive, positively-charged ions are repelled -Balanced at +63mV E =ion 58 mV/ 1 ( log (120/10)
How do we calculate the equilibrium potential?
Nernst equation
what different events are initiated from an action potential that differs between cell types?
Neuron-cellular communication via chemical transmission muscle cell-contraction endocrine cell-secretion
Graded potentials are
Short-lived, localized changes in membrane potential modulation of the membrane potential away from the resting membrane potential of that cell-
Na+/K+ pump (-ATPase):
The low concentration of intracellular Na+ must be actively maintained since Na+ has a strong driving force (i.e both diffusion and electrical potential are driving it into the cell). The pump works against both these concentration and electrical forces. This requires lots of energy to maintain •Consumes 10-40% of available ATP depending on cell type •Single most energy requiring process in the body 3 Na+ pumped out while 2 K+ ions are pumped in
Ohm's law equation
V=IR can be rearranged etc V= potential in volts I = current ( Amps) R = resistance in Ohms states that current between 2 points is equal to the voltage difference between those same two points divided by the resistance
when the cell membrane depolarizes what happens to the voltage-gated potassium channels?
a conformational change occurs and the gates open, these gates open slightly slower than the Na+ channel
capacitance is greater when there is
a narrower separation between conductors. and when the conductors have a larger surface area
What is an action potential?
a rapid, substantial but transient increase in membrane potential ( depolarization) that is propagated (spreading activation)
_________ occurs immediately after the initiation of the action potential. DURING THIS TIME ANOTHER ACTION POTENTIAL CANNOT BE GENERATED
absolute refractory period
__________ immediately follows absolute refractory period and _______
absolute refractory period. lasts for a longer time, DURING THIS TIME A SECOND ACTION POTENTIAL CAN BE GENERATED but only if a stronger stimulus is used
salutatory conduction
action potential jumps from node to node, which speeds up the impulse.
what are the TWO Na+ gates that are involved in the generation of an action potential? where are they located?
activation gate-extracellular side of a membrane- CLOSED at rest inactivation gate-intracellular side of membrane- OPENED at rest
___________ of the voltage changes of membranes tends to be roughly the same across excitable cells
amplitudes
What are some therapeutic effects of modulating voltage-gated K+ channels on Action Potential Frequency?
applying a K channel inhibitor can help bring a decreased frequency of AP firing to a normal level. done for CNS depression, multiple sclerosis applying a K channel activator helps lower an increased frequency of AP firing to a normal neuron action potential firing done for CNS hyperexcitability, seizures, pain, ADHD, anxiety
potassium equilibrium potential
assumption cell membrane is only permeable to potassium aver temp of cat Eion = 62 mV/(1) * log ( 5/ 140) E ion = -84 mV
the excitatory and inhibitory potentials are summed where
at the axon hillock
in neurons action potential propagate via
axons and serve as the basis of neuronal communication
Therapeutic effect of blocking voltage-gated Na+ channels
bock fast voltage-gated SODIUM channels, preventing neuronal depolarization. This blocks the transmission of pain.
movements of ions through channels are driven by and they can
both electrical and chemical forces change the membrane potential ( tho these are small changes measured in mV)
what are the major differences between different cell types and action potential?
both the SPEED and COMPLEXITY of action potentials vary between also initial different events depending on the terminal cell
Myelination increases velocity by decreasing
capacitance and increasing membrane resistance
resting membrane varies based on
cell type, depends on cell-type membrane permeability to specific ions and intracellular concentrations of selection ion species
Depolarize the membrane
change in the cells membrane potential making it more positive ( greater than -70 mV
at resting membrane potential VOLTAGE-GATED Potassiums channels are
closed
high conductance =
decreased resistance
absolute refractory period corresponds to ___________ whereas relative refractory period corresponds to _________
depolarization and repolarization hyperpolarization
V in the cell is
difference in electrical potential energy on either side of the membrane in volts
phase 2 of an action potential initiation
drive force of NA wants to move the membrane towards E(na+) ( = + 60 mV) but before the cell is able to reach this, the increased voltage causes closure of the voltage=gated NA channels . ( sodium flowing in) this also causes the opening of K+ channels this potassium is flowing out of the cell based on its CONCENTRATION GRADIENT
resting membrane potential depends upon what
electric potential difference ion concentration gradient which both work towards equilibrium potential of K , Na and Cl - and the active transport mechanisms present
what is membrane potential in the cell?
electrical potential difference (mV) it is a measured difference between the inside and outside of the cell *FYI The electrode outside the cell is set to zero, so the membrane potential is always relative to the interior of the cell
the steeper the concentration gradient the larger the
electrical potential that balances it needs to be
graded potentials can be either ___ or____ meaning
excitatory, or inhibitory meaning it can either depolarize or hyperbolize the membrane
equilibrium or reversal potential
for an individual ion is the membrane potential (i.e. the voltage as measured inside the cell) where the net flow through any open channels is 0. This indicates that the chemical and electrical forces for that ion are in balance
Z ion charge valence =
for most but not all is 1 (K+ and Na+) or -1 (for Cl-)
the resting membrane potential will be closer to the ion type with
higher permeability
phase 1 ( initiation of an action potential)
induces by depolarization of the resting membrane potential, membrane potential changes in proportion to current amplitude via graded potentials. at some point the cell hits a voltage threshold (specific to cell type usually 15 mv above the cells resting membrane potential) this increase in volage causes voltage-gated Na ion channels to open continuing until all voltage gated Na channels are open deemed depolarization
the phospholipid bilayer is an excellent
insulator
__________ are good conductors in the cell, meaning
intra and extracellular fluid they allow for the flow of charged particles ( as ions are hydrophilic)
lots of drugs focus on changing activity of
ion channels
in neurons and skeletal muscle cells the action of potential initiation occur in
less than 5 ms
membrane potential is largely based on ___ & ___ bec
membrane permeability and electrochemical gradients charged particles are attracted to their opposites chemicals move in area of higher concentration to areas of lower
Hyperpolarization
membrane potential becomes more negative
hyperpolarized membrane
membrane potential becomes more negative than resting potential ( more negative than -70 mV)
how is a voltage gated Na+ channel opened?
membrane potential depolarization causes a Conformational change that flips the gate open. This dramatically increases membrane permeability to Na ions- RESISTANCE IS DECREASED, CONDUCTANCE IS INCREASED
when ion channels are CLOSED they act as ______ when ion channels are open they act as _____
mini resistors conductors
Most excitable membranes are more permeable to ___ due to
potassium due to a greater number of K+ leak channels
immediately after depolarization in the neuron what happens?
potassium leaves the axoplasm via potassium channels (voltage?) repolarizing the axolemma
major ions involved in SETTING and MODIFYING membrane are
potassium, sodium, chloride and calcium
electrical potential energy
potential energy associated with a charge due to its position in an electric field a test charge far away from an opposite charge is said to have high potential energy and it gets closer to the said charge it is said to have low potential energy
interior of the cell at rest is _______ due to
negative . large intracellular anions ( proteins, phosphate, sulfate) that cannot pass through the membrane
Where do action potentials occur?
occur in neuron and muscle cells ( all types skeletal, smooth and cardiac) but these different cell types have unique aspects to certain phases of action potential