Membrane Potentials

The Sodium-Potassium Pump

1.) cytoplasmic Na+ binds to the sodium-potassium pump, the affinity for Na+ is high when the protein is in this shape 2.) Na+ binding stimulates phosphorylation by ATP, donating a phosphate group and making ADP 3.) phosphorylation leads to a conformational change in protein shape, reducing its affinity for Na+ which is released outside 4.) the new shape has a high affinity for K+, which binds on the extracellular side and triggers release of the phosphate group from the cytoplasmic side of the pump 5.) loss of the phosphate group restores the protein's original shape, which has a low affinity for K+ 6.) K+ is released, affinity for Na+ is high again, and the cycle repeats

Goldman-Hodgkin-Katz equation

Goldman-Hodgkin-Katz equation takes into account multiple ions and their respective permeabilities - when channels for more than one ion species are open in the membrane at the same time, the permeabilities and concentration gradients for all the ions must be considered when accounting the membrane potential (the greater the membrane permeability to an ion species, the greater the contribution that ion species will make to membrane potential) . . . this equation will give you a cell's resting membrane potential

ion importance

Na, K, and Cl are present in the highest concentrations, and membrane permeability to each is independently determined (Na and K most important in generating resting membrane potential) - their contributions to the overall membrane potential are a function of their concentration gradients and relative permeabilities (concentration gradients determine their equilibrium potentials, and the relative permeability determines how strongly the resting membrane potential is influenced towards those potentials)

Nernst equation

Nernst equation describes the equilibrium potential for any ion species (the electrical potential necessary to balance a given ionic concentration gradient across membrane so that the net flux of the ion is zero) . . . by comparing the equilibrium potential to resting membrane potential we can figure out which ions are contributing most to the resting membrane potential

The Sodium-Potassium Pump

The Sodium-Potassium Pump and membrane potential - the varying ion permeabilities between Na and K results in a continual efflux of K, negative cell charge, and little influx of Na into the cell . . . now, instead of letting this ever reach equilibrium (where the K will cease to efflux) the cell actively pumps out Na and pumps in K (also contributing to the negative membrane potential, but more importantly keeping K concentration inside the cell higher than outside the cell so it can keep effluxing = vital indirect contribution to membrane potential) . . . this pump makes the cell more negative than it would be from ion diffusion alone

action potential

action potential (as opposed to graded potential): - all-or-none: once membrane has been depolarized to threshold, amplitude is independent of the size of the initiating event - cannot be summed - has a threshold that is usually +15mV depolarized relative to the resting potential - has a refractory period - is conducted without decrement (the depolarization is amplified to a constant value at each point along membrane) - duration is constant for a given cell type under constant conditions - is only depolarizable - initiated by graded potential - mechanism depends on voltage-gated channels

action potential

action potential - because the amplitude of a single action potential does not vary in proportion to the amplitude of the stimulus, an action potential cannot convey information about the magnitude of the stimulus that initiated it (distinguishing between a scream and whisper depends upon the number and patterns of action potentials transmitted per unit time = frequency, not on their magnitude) . . . the action potential can only travel the length of a neuron if each point along the membrane is depolarized to its threshold potential as the action potential moves down axon

action potential propagation

action potential propagation - the membrane is depolarized at each point along the way with respect to the adjacent portions of the membrane (differences between potentials causes currents to flow, depolarizing adjacent membrane) --> current entering is sufficient to easily depolarize adjacent membrane to threshold potential = action potential propagation (sequential opening and closing of Na/K voltage-gated channels) . . . because of this, action potentials do not decrease in magnitude with distance . . . because of propagation, action potential has two choices to either turn back and go through refractory or continue onto polarized membrane (clearly, there is really only one direction)

action potential

action potential: 1.) resting membrane potential is close to the K equilibrium potential because there are more K leak channels than Na channels (higher K permeability) . . . 2.) initial depolarization stimulus via ligand-gated Na channels = graded potential stimulates opening of some voltage-gated Na channels - if membrane reaches critical threshold potential depolarization becomes positive feedback loop (Na influx causes more depolarization, which opens more voltage-gated Na channels) . . . 3.) rapid depolarization of the membrane potential due to open voltage-gated Na channels - actually overshoots so that membrane becomes positive (almost reaches Na equilibrium potential) . . . 4.) as membrane potential reaches peak value the Na permeability abruptly declines as inactivation gates break the cycle of positive feedback and sluggish voltage-gated K channels begin to open (around +30mV) . . . 5. there is a massive efflux of K as the membrane begins to repolarize (repolarization causes Na channels to go from inactivated to closed state = refractory state) . . . 6.) voltage-gated K channels close relatively slowly, so immediately after an action potential there is a period when K permeability remains above resting levels and the membrane becomes hyperpolarized (more negative than resting potential) . . . 7.) all the voltage-gated K channels finally close and the resting membrane potential is restored (negative feedback process)

activated neuromuscular junction

activated neuromuscular junction - when an action potential reaches the presynaptic cell, voltage-gated calcium channel is activated allowing the membrane fusion of the synaptic vesicle to deliver neurotransmitters (acetylcholine) to the neurotransmitter receptor on the muscle cell, ligand-bound receptor opens voltage-gated sodium channels in the muscle cell which triggers the activation of the calcium channel in the sarcoplasmic reticulum . . . calcium goes on to bind with tryptophan = muscle contraction

excitability

alterations in membrane potential = cellular response!! . . . some cells have another group of ion channels other than the channels that establish the resting membrane potential that can be gated under certain conditions (all cells have proteins that establish membrane potential) - 1.) these channels give cell the ability to produce electrical signals that can transmit information between different regions of the membrane = excitability . . . 2.) ligand-gated ion channels (for graded potentials) . . . 3.) charge separation across membrane (which is membrane potential, and something all cells have) . . . these electrical signals can either be graded or action potentials (short distances vs. long distances) . . .

The Sodium-Potassium Pump

an animal cell has a much higher concentration of potassium ions and a much lower concentration of sodium ions, the pump oscillates between two shapes in a cycle that moves 3 Na+ out of the cell for every 2 K+ pumped into the cell = electrogenic pump (moves net charge), the two shapes have different affinities for Na+ and K+, ATP powers the shape change by transferring a phosphate group to the transport protein, maintains a cell's membrane potential

calcium

calcium = Ca^2+, much more concentrated outside the cell as opposed to inside (calcium is sequestered inside cells, you'll never find free-floating calcium ions . . . stored within organelles)

calcium ions

calcium ions - convert the electrical action potential into a chemical signal (neurotransmitter) to travel from the presynaptic cell to the postsynaptic cell . . . happens between synaptic cleft (why nerve impulses aren't happening all the time)

hyperpolarization

change in a cell's membrane potential that makes it more negative - is the opposite of a depolarization, it inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold

channel proteins are highly ion selective

channel proteins are highly ion selective - specificity comes from the structure of the channel and with thermodynamics (how energetically favorable it is for an ion to associate with a particular channel or not) . . . although channels are pores they are gated, so they have a way of determining when and in what direction an ion move

channel proteins are highly ion selective

channel proteins can only move ions down their concentration gradient (no energy required) but the rate of transport is 1000 times faster than that of transporters . . . they have higher impact on membrane potential than transporters do

chlorine

chlorine = Cl-, much more concentrated outside the cell as opposed to inside the cell (negative charge of the cell is coming from the absence of positive charge, not chlorine)

donnan equilibrium

donnan equilibrium = passive movements of ions across semi-permeable membrane to eventually reach equilibrium - takes into account both electrochemical (ionic charges) and diffusive forces (varying ionic concentrations) . . . there are many non-permeating charged particles like large proteins on the insides of cells that contribute to this phenomena - thus, the equilibrium reached results in a balance between the electrostatic and diffusive forces affecting any particular ion (but, there are many non-permeable ions to take into account and the two forces will always offset one another)

donnan equilibrium potential

donnan equilibrium potential - build-up of positive charge in the compartment where sodium cannot move produces an electrical potential that exactly offsets the potassium chemical concentration gradient . . . eventually the membrane potential will become negative enough to produce a flux equal but opposite to the flux produced by the concentration gradient (K moving out via diffusive forces = K moving back in via electrochemical forces) - the magnitude of this equilibrium potential depends on the concentration gradient for that particular ion across the membrane, so the equilibrium potential for one ion species can be different in magnitude and direction from those for other ion species

donnan equilibrium potential

donnan equilibrium potential - the magnitude of this equilibrium potential depends on the concentration gradient for that particular ion across the membrane . . . the larger the concentration gradient, the larger the equilibrium potential becomes because a larger, electrically driven movement of ions will be required to balance the movement due to the concentration difference - why we have the Na/K pump (it keeps the K concentration high so it can keep effluxing)

gated ion channels

gated ion channels are gated in different ways and respond to different types of stimuli - channels can be voltage-gated (change in voltage can open/close gate), ligand gated (by an extracellular or intracellular ligand), or mechanically gated (stretching, compression, vibrations) . . . both ligand and mechanically gated channels cause graded potentials that can serve as initiating stimulus for action potential while voltage-gated channels give the membrane ability to undergo and propagate action potentials

graded potential

graded potential (vs. action potential): - amplitude varies with size of the initiating event - a graded potential can be summed - it has no threshold to meet - there is no refractory period - amplitude decreases with distance = decremental (the flow of charge decreases as the distance from site of origin of graded potential increases) - duration varies with initiating conditions (summation - additional stimulus occur before graded potential dies out, these add to depolarization of first stimulus) - can be depolarization of hyperpolarization - initiated by environmental stimulus (receptor = ligand-gated ion channel), neurotransmitter (synapse), or spontaneously - mechanism depends on ligand-gated channels or other chemical/physical changes

graded potential

graded potentials are changes in membrane potential confined to relatively small region of the membrane, usually produced when some specific change in environment acts on specialized region of the membrane that the cell can pick up . . . the magnitude of the potential charge can vary and be graded - its magnitude is relative to magnitude of this environmental change (charge flows between place of origin and adjacent regions of the membrane with decreasing magnitude = decremental) - local current produces alteration in the amount of charge separation in the membrane regions surrounding the open ion channel (can become more positive or more negative)

ion channels and nerve signaling

ion channels and nerve signaling - action potentials are mediated by voltage-gated cation channels (generating and maintaining them), action potentials allow rapid long-distance communication along axons, voltage-gated calcium channels in nerve terminals convert an electrical signal into a chemical signal, and transmitter-gated ion channels in the post-synaptic membrane convert the chemical signal back into an electrical signal

ion permeability

ion permeability - determined by number of specific ion channels embedded in plasma membrane . . . most cells have more K-leak channels than Na-leak channels - thus K can move across cell membrane much more easily than Na can (K wants to move outside of cell because it has a much lower concentration outside than inside - there are a lot of pumps that let K continually efflux out of the cell, establishing negative membrane potential) . . . Na wants to move inside cell, but there aren't many ion channels that let Na cross

ion importance

ions are essential to the cell for generating the membrane potential of a cell (voltage difference between the immediate sides of a membrane), which provides energy for the cell to do work and allow the cell to be responsive to changes in its environment, used to transmit signals across cells, maintained by both transporters and channel proteins

lambda equation for current's speed

lambda equation for current's speed - tells you how fast current is moving through system = distance along plasma membrane (point along membrane current can travel before it can be reduced by 63%) . . . big lambda is good = increased propagation . . . lambda = square root(resistance across membrane / resistance across length of neuron) - in this equation the lambda takes into account both the resistance across the membrane that can be increased by myelination and the cross-sectional resistance that can be decreased with greater axon diameters

nerve cell

nerve cell - voltage-gated calcium channels in presynaptic nerve terminals convert an electrical action potential into a chemical signal . . . transmitter-gated ion channels (opened by binding of specific neurotransmitters) in the postysynaptic membrane convert chemical signal back into an electrical action potential

resting membrane potential

neuron - during the resting membrane potential, we are negative inside the axon and both sodium and potassium channels are closed . . . depolarization, sodium channels are opened while potassium channels are closed . . . after the peak action potential is reached repolarization occurs, where potassium channel is open and sodium channel is closed . . . hyperpolarization = leaky potassium channels, making sure that cell doesn't revert back to a membrane potential

overshoot

overshoot - reversal of the membrane potential polarity (when the inside of the cell becomes positive relative to the outside) . . . process during the action potential when sodium is rushing into the cell causing the interior to become more positive

potassium

potassium = K+, more concentrated inside the cell as opposed to outside the cell

potassium equilibrium potential

potassium equilibrium potential - when both concentration and charge are equal on both ends = equilibrium . . . this will never happen in a cell, if every ion in the cell were in equilibrium than we wouldn't have charges that would be in equilibrium and vice versa - if we were in fact in equilibrium we wouldn't have any potential energy to utilize - the cell works really hard to not allow this equilibrium to be reached . . . when both concentration and charge are equal on both ends - this will never happen in a cell, if every ion in the cell were in equilibrium we wouldn't have any potential energy to utilize

potassium leak channel

potassium leak channel - located in plasma membrane of most animal cells, maintenance of resting membrane potential . . . generates resting membrane potential, efflux of K out of the cell, making inside of cell negative

depolarization

process during the action potential when sodium is rushing into the cell causing the interior to become more positive - voltage change that occurs when the difference in charge across a membrane decreases . . . thus membrane is depolarized when its potential becomes less negative

protons

protons = H+, slightly more concentrated in the cell as opposed to outside the cell (slightly more acidic inside the cell)

refractory periods

refractory periods limit number of action potentials an excitable membrane can produce in a given period of time - contribute to the separation of action potentials so that individual electrical signals pass down axon, key in determining direction of action potential propagation . . . during the action potential, a second stimulus will not produce a second action potential = absolute refractory period (occurs during period when voltage-gated Na channels are either already open or have proceeded to the inactivated state during first action potential --> inactivation gate must be removed by repolarizing membrane and closing pore before channels can reopen to second stimulus)

refractory periods

refractory periods limit number of action potentials an excitable membrane can produce in a given period of time - contribute to the separation of action potentials so that individual electrical signals pass down axon, key in determining direction of action potential propagation . . . following absolute refractory period there is an interval during which a second action potential can be produced, but only if the stimulus is considerably stronger than the original (cell is hyperpolarized, so very strong stimulus required - some but not all Na channels have returned to resting state and some K channels are closed but not all), magnitude of action potential isn't nearly as high

resting membrane potential

resting membrane potential - all cells have this potential difference across plasma membrane under resting conditions . . . membrane potential stated in terms of cell, which is negative (whether it be -5 or -90 depending upon the cell type) . . . excess of negative charges inside cell attracted to excess positive charges of outside cell, creates thin shell of voltage (which is why the membrane potential only covers small amount of area across membrane - collectively the cell is neutral, as is the extracellular fluid)

resting membrane potential

resting membrane potential = sodium channel closed, 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 . . . electrical voltage difference across the membrane at rest, negative ions along inside of cell and positive ions along outside of cell

resting neuromuscular junction

resting neuromuscular junction - presynaptic cell that governs the movement of that particular muscle cell is not receiving a signal with vesicle full of neurotransmitters (acetylcholine), calcium channels are closed, neurotransmitter receptor is muscle cell is inactivated, and calcium in the muscle cell is stored in the sarcoplasmic reticulum

repolarization

return of the cell to resting state, caused by re-entry of potassium into the cell while sodium exits the cell . . . after Na+ ions have rushed into the cell, K+ ions rush out of the cell to restore the balance and the original polarity (sodium/potassium pump)

sodium

sodium = Na+, less concentrated inside the cell as opposed to outside the cell

action potential propagation

speed of action potential propagation depends on two variables . . . 1.) cross-sectional resistance - the larger the nerve fiber diameter, the faster the action potential propagates (large fiber offers less internal resistance to local current - more ions will flow in a given time, bringing adjacent regions of membrane to threshold faster) . . . 2.) myelination - myelin is an insulator that makes it more difficult for charge to flow between intracellular and extracellular fluid (increases resistance, less leakage, local current can spread farther along an axon), action potentials can only occur at the nodes of Ranvier where concentration of voltage-gated Na channels are high (saltatory conduction - membrane pumps need to restore fewer ions)

dendrites

the dendrites of a neuron will receive a signal, there is a localized depolarization in the body - when it reaches a certain threshold that depolarization is extended to the axon of the neuron, action potential is then transmitted from one region of the neuron to another

resting membrane potential

the development of the resting membrane potential includes - 1.) action of the Na/K pump sets up the concentration gradients for Na and K (concentration gradients determine the equilibrium potentials for these two ions - value to which each ion would bring the membrane potential) . . . 2.) greater efflux of K out of the cell than influx of Na inside the cell due to the number of K ion channels and its greater permeability (this eventually nears potassium's equilibrium potential) . . . 3.) before equilibrium can be established, the Na/K pump works on reestablishing the concentration gradients between both ions so K keeps effluxing out of the cell

resting membrane potential

the magnitude of the resting membrane potential depends on two factors - 1.) differences in specific ion concentrations in the intra/extracellular fluids = Nernst equation and equilibrium potential!! (ion pumps embedded in membrane and/or donnan equilibrium - passive movement of ions across cell membrane) . . . 2.) differences in membrane permeabilities to the different ions, which reflect the number of open channels for the different ions in the plasma membrane (the greater the number of open ion channels, the greater an ion's permeability)

membrane potential

the membrane potential is governed by the permeability of a membrane to specific ions, ion flow it driven by the electrochemical gradient of that specific ion, electrochemical gradients are a combination of two influences - voltage gradient of the ion across the membrane (the actual charge of the ion) and the concentration of the ion across the membrane

membrane potential

the membrane potential spans a membrane and contributes voltage difference immediately above and below that membrane . . . the cytosol immediately under the membrane has a negative charge while right on the outside of the cell there's a positive charge . . . depending on different cell types you'll have different voltages

negative charge

the negative charge of the cell is attributed to the presence of many other anions within the cell, specifically carbonates, phosphates, proteins, nucleic acids, metabolites carrying phosphate and carboxyl groups (most free-floating things are negatively charged because cytosol cannot support uncharged molecules) . . . it takes a lot of energy to do this so the membrane potential is maintained by the movement of cations

cell's response

the signal never determines the cell's response, but rather the receptors do . . . there are many chemical signals that act on the same receptor or the same chemical signal that acts on many different chemical receptors in different differentiated cells

threshold stimuli

threshold stimuli (graded potential) - not all membrane depolarizations in excitable cells trigger positive feedback process that leads to an action potential, they only occur when the initial stimulus plus the current through the Na channels are sufficient to elevate membrane potential beyond the threshold potential (about 15mV less negative than resting membrane potential) . . . at depolarizations less then threshold the membrane will return to its resting level as soon as the stimulus is removed (subthreshold potentials caused by subthreshold stimuli) - once threshold is reached, the membrane events no longer rely upon stimulus strength --> all-or-none

voltage-gated potassium channel

voltage-gated K channel - located in plasma membrane of nerve cell axon, return of membrane to resting potential after initiation of an action potential . . . they are very sluggish and respond less than accordingly to a change in membrane potential . . . exert negative feedback - depolarization of Na influx causes K channels to open, increasing K permeability and its efflux out of cell, repolarizing the membrane and shutting the channels down

voltage-gated Na channels will have three possible conformations

voltage-gated Na channels will have three possible conformations - the fault conformation = closed conformation (closed during negative resting membrane potential), if there's a graded potential that depolarizes the cell enough to cross threshold than the Na channels will open, soon after depolarization the inactivation gate will close (refractory period), and then when the cell begins to repolarize the channels close, forcing the inactivation gate back out . . . these conformations assure that the signal will only go when activated and in one direction

voltage-gated calcium channel

voltage-gated calcium channel - convert an electrical action potential into a chemical signal, happens between pre and post-synaptic cells . . . once action potential reaches presynaptic nerve terminal, voltage change opens-up calcium channels which activates the fusion of a synaptic vesicle full of neurotransmitters with the plasma membrane of the synaptic cleft with postsynaptic cell receptors that interpret chemical signal

voltage-gated calcium channel

voltage-gated calcium channel - located in the plasma membrane of nerve cell terminal, stimulation of neurotransmitter release

voltage-gated sodium channel

voltage-gated sodium channel - located in plasma membrane of nerve cell axon, generation of action potential (inactive when cell is at negative resting potential) . . . 1.) respond much faster to changes in membrane voltage then voltage-gated K channels (open to sudden depolarization far sooner than K channels, and the K channels will close much slower when membrane becomes repolarized) . . . 2.) Na channels have an extra feature in their structure known as the inactivation gate (limits influx of Na ions by blocking channel shortly after depolarization opens it) . . . exert positive feedback - depolarizing stimulus open voltage gated Na channels, increased permeability of Na to influx into cell, depolarizing membrane even more and opening more Na channels

voltage-gated Na channels will have three possible conformations

voltage-gated sodium channels will have three possible conformations - they allow not only to propagate the signal but to also direct the signal = closed --> open --> inactivated --> closed . . . we start with a closed channel, polarize it to activate it, then inactivate those channels (by putting sodium into equilibrium around micro-environment) to propagate signal forward in the direction we want