Physiology Chapter 5: Membrane Potentials and Action Potentials

net driving force on ions

-difference in mV between the membrane potential (Vm) and the equilibrium potential for that ion (Eion)

equlibrium potential (E_)

-electrical potential that counters net diffusion of an ion -if outside is much greater than inside than E will be positive

repolarization

-going from postitive/less negative back down towards normal resting potential -return to RMP

action potential

-is a regenerating depolarization of membrane potential that *propagates* along an *excitable* membrane. -All-or-none event (need to reach threshold) -Constant amplitude (do not summate) -Initiated by depolarization -Involve changes in permeability -Rely on voltage-gated ion channels

Excitability

-range in which RMP changes before there is an action potential generated (double check). (between RMP and threshold) -range between hyper and depolarization -ability to generate action potential

What is the Nernst potential?

The diffusion potential level across a membrane that exactly opposes the net diffusion of a particular ion through the membrane

The inactivation of sodium channels. The period occurs between inactivation of the sodium channels and resting.

What, in particular, causes an the absolute refractory period to not allow any other action potential to occur?

the difference between the potentials inside and outside the cell

When using a microelectrode to measure a membrane potential, the measurement that the device yields is representative of what?

Measuring the Membrane Potential

A small pipette filled with an electrolyte solution is impaled through the cell membrane in the the interior of the fiber. Another electrode called the "indifferent electrode" is placed in the extracellular fluid The potential difference between the inside and outside of the fiber is measured using an appropriate volmeter. As long as the electrode is outside the nerve membrane, the recorded potential is zero, which is the potential of the extracellular fluid. As the recording electrode passes through the voltage change area at the cell membrane, the potential decrease abruptly to -90 millivolts. Moving across the center of the fiber, the potential remains at a steady -90 millivolt level but reverses back to zero the instant it passes through the membrane on the opposite side of the fiber. *To create a negative potential inside the membrane, only enough positive ions to develop the electrical dipole layer at the membrane itself must be transported outward.

voltage-gated Na+ and K+ pumps

Action potentials are largely a function of the behavior of what?

slower

After Na+ channels become inactive after an action potential, K+ channels become activated but have a much ______________ effect

An action potential is

a regeneration depolarization of membrane potential that propagates along an excitable membrane

Overshoot

action potential actually having a positive value - occurs in large nerve fibers

Channel leaks

allow for K+ to go back on the outside of the cell, and Na+ to the inside of the cell using simple diffusion

Nernst Potential

also called Resting Membrane Potential - relation of diffusion potential to ion concentration difference across a membrane Depends on 3 Factors: 1. charge of ions 2. permeability of membrane to each ion 3. concentration of ions

Repolarization

becoming more negative Ex) Na+ channels close and K+ channels open and K+ can leave the cell and make the cell more negative again

Depolarization

becoming more positive Ex) membrane becomes more permeable to Na+ b/c gates open and Na+ can come in

excitable

capable of generating action potentials

propagates

conducted without decrement (an 'active' membrane event)

most voltage gated channels open in response to

depolarization

net driving force on any ion

difference in millivolts between the membrane potential (Vm) and the equilibrium potential for that ion (Eion).

Action potentials allow for

electrical communication

Diffusion Potential

electrical difference between inside and outside of cell d/t concentration gradient Ex) Na+/K+ pump

Voltage Gated K+ Channel

gate is closed at rest - has slow activation - as interior of cell becomes less negative a conformational opening of gate occurs slowly and K+ diffuses outwards - d/t delay K+ channel opens at the same time Na+ channel starts to close b/c of inactivation and this combining factor speeds repolarization

Resting membrane potential is closest to

resting membrane of potassium because it is inside the cell

non-selective cation channels

some channels are only selective for cations (also some can be for just specific ions) (pos)

Action Potential

something causes a change from RMP to a + potential and then rapidly go back to - potential

Mylelin ________ up signal transmission

speeds up

schwann cells

surround the nerve axon forming a myelin sheath

What is a synapse?

the junction between the axon tip of the sending neuron and the dendrite or cell body of the receiving neuron; where neurotransmitters are released

membrane potential

the voltage difference across a membrane

Threshold

usually -65

deactivation of gate

when membrane depolarizes

Contribution of the K+ Diffusion Potential

Because of the high ratio of K+ ions inside to outside 35:1, the Nernst potential corresponding to this ratio is -94 millivolts because the log of 35 is 1.54, and this multiplied by -61 millivolts is -94 millivolts. If K+ ions were the only factor causing the resting potential, the resting potential inside the fiber would be equal to -94 millivolts

How are nerve signals transmitted?

By action potentials, which are rapid changes in the membrane potential that spread rapidly along the nerve membrane fiber. Each action potential begins with a sudden change from the normal resting negative membrane potential to a positive potential and ends with an almost equally rapid change back to the negative potential.

How is the magnitude of the Nernst potential determined?

By the ratio of the concentration of that specific ion on the two sides of the membrane. The greater the ratio, the greater the tendency for the ion to diffuse in one direction, and therefore the greater the Nernst potential required to prevent additional net diffusion.

Each action potential begins with a sudden change from the normal resting membrane potential to a positive potential and ends with an almost equally rapid change to the negative potential.

Explain the how each action potential begins and ends.

It is the the phase at the end of an action potential where the membrane potential goes below normal resting levels due to slowed inactivation of K+ channels

Explain what afterhyperpolarization is

The membrane is far more permeable to K+. Increased K permeability is due to K lead channels allowing K to go in and out of the membrane whenever. (flows more out than in)

If membrane potential for K+ is -94mv and membrane potential for Na+ is +61mV, why then is the normal resting membrane potential -90mV?

roughly the same time when Na+ channels close

In order to bring a membrane potential back to normal resting levels, when do K activation channels open?

Inactivation Gate

Inside of membrane - slow to close, when closes Na+ can no longer come in - starts to slowly close when activation gate snaps open - when gate closes it will not reopen until RMP returns to -90mV

Which ion has greatest affect on membrane potential?

K+ b/c it is more permeable sets the resting membrane potential because it is more negative than Na+

Schwann

Myelin sheaths are composed of ___________ cells.

Gradients for Na+ and K+ across the resting nerve membrane

Na+ outside: 142 mEq/L Na+ inside: 14 mEq/L K+ outside: 4 mEq/L K+ inside: 140 mEq/: The ratios of these two respective ions from the inside to the outside are: Na+ inside/Na+ outside= 0.1 K+ inside/ K+ outside= 35.0

Absolute refractory period:

No matter what will not depolarize

The 2 gates of the voltage-gated sodium

One near the outside of the channel called the activation gate. Another near the inside called the inactivation gate The activation gate is closed when the membrane potential is in the normal resting membrane at -90 millivolts. This prevents entry of Na+ to the interior of the fiber.

Activation Gate

Outside of membrane - Na+ can come into cell - conformational change opens completely as RMP becomes less negative (-70 to -50mV)

myelination

Rate of action potentials is highly related to amount of ___________ in an axon.

What happens to sodium during repolarization

Sodium is pumped out of the cell

What happens to sodium during depolarization?

Sodium which is usually on the outside of the cell rushes into the cell

overshoot

-crosses 0mV and goes into positive -variable (more likely with large fibers) -anytime its positive

Depolarization

-change from resting negative (most negative) towards positive (becoming more positive or becoming less negative) - doesn't always lead to action potential, still need to reach threshold

KNa (equilibrium potential)

+61

resting membrane potential of smooth muscle fibers

-50 to -60mV

resting membrane potential of neurons

-60 to -70 mV

Resting membrane potential

-70mv to -90mv

resting membrane potential of skeletal muscle fibers

-85 to -95 mV

Normal RMP of nerve fibers

-90mV occurs because of large concentration gradients of Na+ and K+ d/t the sodium/potassium pump

Ek (equilibrium potential)

-94

threshold

-MP at which the cell needs to reach in order for AP to be generated

absolute refractory period

-Second AP is not possible regardless of strenght/duration of stimulus -Na Inactivation gates are still closed, and K activation gate is open

Hyperpolarization

-The movement of the membrane potential of a cell away from rest potential in a more negative direction. -more negative (downward deflection), less positive -if the membrane is at any point below its normal resting

Differences Across a Selectively Permeable Membrane:K+

1. K+ concentration is great inside nerve fiber membrane by very low outside the membrane 2. The membrane is permeable to K+ ions but not any other ions 3. There is a large K+ concentration gradient from inside toward outside (K+ like to be in extracellular fluid) 4.Strong tendency for extra K+ ions to diffuse outward through membrane 5. As they do, they carry the positive ions outside the membrane creating electropositivity outside and the inside of the membrane now has electronegativity because of the anions that do not diffuse outwards 6. The potential difference between the inside and outside is called diffusion potential. 7. This potential becomes so great it blocks any further net K+ diffusion to the outside of the membrane even though there is still a high K+ concentration gradient. 8. In the normal mammalian nerve fiber, the potential difference is about 94 millivolts, with negativity inside the fiber membrane.

Key points from the Goldman equation

1. Na+, K+ and Cl- are the most important ions involved in the development of membrane potentials in nerve and muscle fibers, as well as in the neuronal cells in the nervous system. 2. The quantitative importance of each of the ions in determining the voltage is proportional to the membrane permeability for that particular ion. Ex. If the membrane ha zero permeability to K+ and Cl- ions, the membrane potential becomes entirely dominated by the concentration gradient of the Na+ ions alone and the resulting potential will be equal to the Nernst potential for Na+ 3. A positive ion concentration gradient from inside the membrane to the outside causes electronegativity inside the membrane. The opposite effect occurs when there is a gradient for a negative ion. A Cl- ion gradient from outside to the inside causes negativity inside the cell while leaving the nondiffusible positive ions on the outside. 4. The permeability of the Na+ and K+ channels undergoes rapid changes during transmission of a nerve impulse, whereas the permeability of the Cl- channels does not change greatly during this process.

Depolarization Stage

1. The membrane suddenly becomes permeable to Na+ ions allowing tremendous numbers of positively charged Na+ ions to diffuse to the interior of the axon. 2. The normal "polarized" state of -90 millivolts is immediately neutralized by the inflow of + charged Na+ ions, with the potential rising rapidly in the positive direction 3. In large nerve fibers, the great excess of + Na+ ions moving to the inside causes the membrane potential to "overshoot" beyond the zero level and to become somewhat positive. In smaller fibers the potential merely approaches the zero level and does not overshoot to the + state.

When a membrane is permeable to several different ions, the diffusion potential that develops depends on 3 factors:

1. The polarity of the electrical charge of each ion 2. The permeability of the membrane (P) to each ion 3. The concentration (C) of the respective ions on the inside (i) and outside (o) of the membrane.

Differences Across a Selectively Permeable Membrane: Na+

1. There is a high concentration of Na+ ions outside the membrane and low concentration of Na+ ions inside the cell 2. The membrane this time is highly permeable to the Na+ ions and impermeable to all other ions. 3. The positively charge Na+ ions diffuse inside creating electropositivity inside the the membrane fiber and electronegativity outside the membrane 4. The membrane potential rises high enough to block further net diffusion of Na+ ions to the inside 5. This time, in the mammalian nerve fiber, the potential is about 61 millivolts positive inside the fiber

Repolarization Stage

1. Within a few seconds after the membrane becomes highly permeable to Na+ ions, the Na+ channels begin to close and the K+ channels open to a greater degree than normal. 2. Rapid diffusion of K+ ions to the exterior re-establishes the normal negative resting membrane potential.

What are the basics of action potentials?

1. all or none event 2. constant amplitude 3. involve changes in permeability 4. rely on voltage gated ion channels

What 3 factors affect the resting membrane potential?

1. charge of ions 2. permeability of membrane to each ion 3. concentration of ions

Synapses can be

1. excitatory or (acetylcholine, glutamate) 2. inhibitory ( GABA, glycine)

Voltage-gates Na+ Channel

2 gates: activation and inactivation

Leakage of K+ through the nerve cell membrane

A channel protein, sometimes called a tandem pore domain or K+ "leak" channel, in the nerve membrane through which K+ can leak even in a resting cell. The K+ leak channels may also leak Na+ ions but are much more permeable to leak K+

membrane potential

A ion concentration difference across a selectively permeable membrane can create a __________________ ___________________

node of ranvier

A myelin sheath is interrupted ever 1-3mm by a ______________________________.

Absolute: depolarization and repolarization Relative: afterhyperpolarization

What other phase of the action potential occurs at the same time of the absolute refractory period? of the relative refractory period?

The Nernst Equation

The equation can be used to calculate the Nernst potential for any univalent ion at the normal body temperature of 98.6 F (37 C) EMF(millivolts) = +/- 61/z x log concentration inside/concentration outside EMF is electromotive force and z is the electrical charge of the ion (+1 for K+) 1. When using this formula, it is usually assumed that the potential in the extracellular fluid outside the membrane remains at zero potential, and the Nernst potential is the potential inside the membrane. 2. The sign of the potential is positive (+) if the ion diffusing from the inside to the outside is a negative ion. 3. The potential is negative (-) if the ion diffusing from the inside to outside is positive. * When the concentration of positive potassium ions on the inside is 10 times that on the outside, the log of 10 is 1, so the Nernst potential calculates to be -61 millivolts inside the membrane.

Na+-K+ Pump

The pump continually transports Na+ ions to the outside of the cell and K+ ions to the inside. This is an electrogenic pump because more + charges are pumped to the outside (3 Na+ outside for every 2 K+ ions inside) This causes a negative potential inside the cell membrane.

Contribution of the Na+-K+ pump to the normal resting membrane potential

The pumping of more Na+ ions to the outside than the K+ ions being pumped to the inside causes continual loss of positive charges form inside the membrane, creating an additional degree of negativity (about -4 millivolts additional) on the inside beyond that which can be accounted for by diffusion alone The diffusion potential alone caused by potassium and sodium diffusion would give a membrane potential of about -86 millivolts, with almost all of this being determined by K+ diffusion An additional -4 millivolts is then contributed to the membrane potential by the continuously acting electrogenic Na+-K+ pump, giving a net membrane potential of -90 millivolts

What is the resting stage?

The resting membrane potential before the action potential begins. This membrane is said the be "polarized" during this stage because of the -90 millivolts negative membrane potential that is present.

Resting Membrane Potential of Neurons

The resting membrane potential of large nerve fibers when they are not transmitting nerve signals is about -90 millivolts. The potential inside the fiber is 90 more negative than the potential in the extracellular fluid outside the fiber.

Voltage-Gated Na+ and K+ channels

The voltage-gated Na+ channel is the necessary actor in causing both depolarization and repolarization of the nerve membrane during the action potential. A Voltage-Gated K+ channel also plays an important role in increasing the rapidity of repolarization of the membrane.

Contribution of Na+ Diffusion through the nerve membrane

There is an addition of slight permeability of the nerve membrane to Na+ ions, caused by the minute diffusion of Na+ ions through the K+-Na+ leak channels The ratio of Na+ ions from inside to outside the membrane is 0.1, which gives the calculated Nernst potential for inside of the membrane of +61 millivolts.

How do the Na+ and K+ potentials interact with each other, and what will be the summated potential?

This can be answered by using the Goldman equation. If the membrane is highly permeable to K+ but only slightly permeable to Na+, it is logical that the diffusion of K+ contributes far more to the membrane potential than does the diffusion of Na+. In the normal nerve fiber, the permeability of the membrane to K+ is about 100 times as great as its permeability to Na+ Using this value in the Goldman equation gives a potential inside the membrane of -86 millivolts, which is near the K+ potential

Goldman equation

This formula gives the calculated membrane potential on the inside of the membrane when two univalent positive ions, Na+ and K+, and one univalent negative ion, Cl-, are involved.

if you increase permeability of Na or K what happens to Vm

Vm moves closer to the E potential of either Na/K -would be a larger change for Na than K

Non-myelinated: 0.25m/s Myelinated: 100 m/s

What are the approximate velocities of action potentials in non-myelinated and myelinated axons?

Site of AP to physically occur, increases AP velocity, energy conservation, allows signals to "hop"

What are the functions of the nodes of Ranvier?

K+: -94mV Na+: +61mV

What are the membrane potentials for K+ and Na+ respectively?

1. Diffusion of K+ alone 2. Diffusion of K+ and Na+ 3. Diffusion of K+ and Na+ with movement of both ions using the K-Na pump

What are the three conditions in which a resting membrane potential can be established?

The opening and closing of Na+ activation/inactivation gates as well as the opening and closing of K+ activation gates.

What dictates the initial change of a membrane potential becoming positive/negative?

The principle that an action potential always goes to completion once it is initiated.

What is the All-or-None principle?

Demyelinating of the CNS

What is the cause of Multiple Sclerosis

Absolute: Period of time where it is impossible for another action potential to occur no matter how large the stimulus Relative: Period of time where a second action potential can be generated but requires a stimulus that is greater than normal

What is the difference between absolute and relative refractory period?

Period of time during an action potential where the frequency of other action potentials to occur is lower.

What is the refractory period?

The membrane potential at which an action potential is initiated

What is threshold potential?

Relative refractory period:

needs a bigger impulse to depolarize the cell

Permeability of axon membrane to ions is determined by the:

number of open channels

Membrane Potential

occurs d/t concentration gradient of selectively permeable substances

Nerve Action Potential

rapid changes in membrane potential that spread rapidly along nerve fiber