Anatomy 312 Review Final - Chapter 12 - Graded Potentials and Action Potentials

What causes changes in membrane potential

1. Changes in Membrane potential act as signals

   1. Neurons use changes in membrane potential as communication signals

   2. Changes in membrane potential can be produced by:

      1. Changes in membrane permeability to any ion, or

      2. Changes in ion concentrations on the two sides of the membrane

   3. Only permeability changes are important for information transfer

   4. Changes in membrane permeability is due to the opening or closing of ion channels

Ion channels in membrane

1. Ion channels in plasma membrane

   1. Not always open, contain a gait

   2. Gate must receive a signal to open (ligand binding, change in voltage, stretch)

   3. Direction of movement determined by electrochemical gradient

   4. Selective or non-selective

2. Chemically gated ion channels – a.k.a. ligand-gated ion channels – opens when a chemical (e.g. neurotransmitter) binds to its receptor

3. Voltage-gated ion channels – open and close in response to changes in membrane potential – e.g. voltage-gated Na+ channels open in response to membrane depolarization

4. Stretch-Activated ion channels – mechanosensitive channels – open in response to physical deformation to the channels

Depolarization

membrane potential becomes less negative than RMP; a reduction in MP

Overshoot

refers to a reversal of the membrane potential polarity

Repolarization

membrane potential returns to its resting value (RMP)

Hyperpolarization

membrane potential becomes more negative than the RMP; an increase in MP

RMP

resting membrane potential

a cell is “polarized” because…

its interior is more negative than its exterior

Graded Potentials (or local potentials)

• transmit information only over short distance

  1. Localized changes in membrane potential, confined to a relatively small region of the plasma membrane

     1. Ex: positive ions (e.g. Na+) flow into cell via a ligand-gated ion channel and depolarize the membrane adjacent to the channel

     2. Graded potentials are generated by opening of chemically-gated ion channels or stretch-activated ion channels

Action Potentials

1. transmit information over very long distance

   1. Brief change in membrane potential that can propagate along the surface of excitable cells

   2. Action potential is different from graded potential due to the opening of voltage-gated ion channels in the cell membrane

   3. Voltage-gated ion channels are regulated by membrane potential; they are closed when the cell is at resting membrane potential, and opened when the cell is sufficiently depolarized

   4. Cells that can generated action potentials are called excitable cells (e.g. neurons, muscles, and gland cells)

Excitable cell

1. Cells that can generate action potentials

2. Ex: neurons, muscles, and gland cells

Characteristics of graded potentials

1. Graded potentials can be depolarization or hyperpolarization

2. The size of a graded potential is proportional to the size of the stimulus

3. Graded potentials decrease in magnitude with increasing distance from the site of origin – decremental

4. Where do they occur?

   1. Receptor region of a sensory neuron

      1. Changes in the cell’s environment (e.g. light, smell, sound, touch) act on a specialized region of the membrane, include changes in membrane potential

      2. Due to opening of chemically-gated or stretch-activated ion channels

      3. Known as. Receptor potentials

   2. Dendrites and cell body of an interneuron or a motor neuron

      1. Release of neurotransmitters causes the changes in membrane potential

      2. Due to opening and chemically-gated ion channels

      3. Known as synaptic potentials

Resting state - ion movement

1. Voltage-gated Na+ and K+ channels are closed

2. Only the leak channels are open, maintaining resting membrane potential.

   1. Voltage-gated Na+ channels are closed

   2. No Na+ ions moving in or out through voltage-gated Na+ channel

   3. Voltage-gated K+ channel closed

   4. No K+ ions moving in or out through voltage-gated K+ channel

Local potential and threshold - ion movement

1. A local potential induced by a stimulus (e.g., release of a neurotransmitter) is needed to bring the membrane potential to the threshold (~-55 mV)

2. The threshold is the minimum needed to open voltage-gated ion channels

Depolarization - ion movement

1. Voltage-gated Na+ channels open. Na+ rushes into the cell and further depolarizes the membrane

2. Voltage-gated Na+ channel open

3. Na+ ions move in through the voltage-gated Na+ channel

4. Voltage gated K+ channel is closed

5. K+ ions do not move in or out through the voltage-gated K+ channel

   1. Positive feedback cycle for opening of voltage-gated Na+ during depolarization

      1. Threshold level stimulus applied à depolarization (decreased membrane potential) – subthreshold level stimulus will not active the positive feedback cycle à opening of some voltage gated Na+ channels à Influx of Na+ (which further decreases membrane potential).

      2. The positive feedback cycle stops when all voltage-gated Na+ channels are open

Overshoot - ion movement

1. Membrane potential further depolarizes and actually becomes positive with respect to ECF resulting in overshoot

2. The polarity of membrane potential reverses

3. AP peaks at ~+30 mV

4. Membrane potential approaches Ena (~+60mV) as PNa is about 1,000 times greater than in resting state

Repolarizing phase - ion movement

1. When action potential reaches the peak, Na+ channels become inactivated and PNa decreases drastically

2. With some delay after the onset of the action potential, voltage-gated K+ channels begin to open (they are sometimes called delayed K+ channels). K+ ions flux out of the cell, which helps the membrane repolarize rapidly.

Hyperpolarization - ion movement

1. The voltage-gated K+ channels close relatively slowly. After AP occurs, PK remains above resting levels, causing transient membrane hyperpolarization. This is called after-hyperpolarization

2. Voltage-gated Na+ channel begin to reset back to closed state

Where action potential is initiated in multipolar neuron

1. Propagates down the length of the axon to axon terminals

2. Begins in axon terminals of other cell and comes through dendrites down to axon and to axon terminals.

Threshold stimuli

Not all initial stimuli (e.g. graded potentials) are sufficient to evoke an action potential. The stimulus that is just large enough to evoke an action potential is called a threshold stimulus.

Subthreshold stimuli

stimuli that are too weak and do not generate a potential

subthreshold potentials

weak depolarizations

All-or-none feature of an action potential

1. Stimuli that are larger than threshold stimulus elicit action potentials of exactly the same amplitude as those caused by threshold stimulus

2. Action potentials either occur maximally or not at all (all-or-none)

what would happen to the action potential if voltage-gated Na⁺ channels were blocked (e.g. by tetrodotoxin)?

Does not allow action potentials to generate or propagate 

Absolute refractory period

1. During a period of an AP, a second stimulus, no matter how strong, will not produce a second AP

2. This is because the voltage-gated Na+ channels are either already open or in the inactivated state.

3. The voltage-gated Na+ channels can’t re-open unless they are in the closed state.

Relative refractory period

1. The period of time following absolute refractory period

2. During this period, a second AP can occur, but only with a larger-than-threshold stimulus.

3. Why?

   1. Some Na+ channels have returned to the closed state and can be re-opened

   2. Membrane is hyperpolarized because K+ channel is still open. Larger magnitude of stimulus is needed to reach threshold.

Coding for stimulus intensity

1. All Aps are alike. The amplitude of AP is independent of stimulus intensity

2. Strong stimuli can generate Aps more often then weaker stimuli in a given time interval

3. The CNS determines stimulus intensity by the frequency of APs

How action potentials are propagated along an axon

1. An action potential is generated as sodium ions flow inward across the membrane at one location

2. The depolarization of the first action potential has spread to the neighboring region of the membrane, depolarizing it and initiating a second action potential. At the site of the first action potential, the membrane is repolarizing as K+ flows outward

3. A third action potential follows in sequence, with repolarization in its wake. In this way, local currents of ions across the plasma membrane give rise to a nerve impulse that passes along the axon.

Factors that determine the speed of action potential propagation

1. Axon diameter

   1. Larger diameter axons >>smaller diameter axons

2. Axon myelination:

   1. Myelinated axons >> unmyelinated axons

      1. In unmyelinated axons, Aps are generated continuously along the axonal membrane (continuous conduction)

      2. In myelinated axons, Aps are triggered only at the nodes of Ranvier (saltatory conduction)

         1. Myelin-forming cells (glial cells) cover about 1 mm of axon length. In between are gaps called the nodes of Ranvier

         2. High density of voltage gated Na+ channels are found at nodes of Ranvier

         3. Aps jump from node to node

Conduction velocity

0.5m/s (small diameter, unmyelinated) to 100m/s (large diameter, myelinated, 20 ms from head to toe

Multiple sclerosis

1. Demyelination in the CNS

2. Autoimmune disease

3. The myelin sheath, which is a protective membrane that wraps around the axon of a nerve cell, is destroyed with inflammation and scarring.

Guillain Barre syndrome

1. Demyelination in the PNS

2. Autoimmune disorder

3. Usually triggered by an acute infectious process

Type A nerve fiber

1. transmit sensory information on position, balance, and delicate touch and pressure sensation from skin. They also carry motor commands to skeletal muscle

   1. 4-20 um diameter

   2. Myelinated

   3. 150 m/sec conduction speed

Type B nerve fiber

1. transmit sensory

   1. 2-4 um diameter

   2. Myelinated

   3. 15 m/sec conduction speed

Type C nerve fiber

transmit sensory

1. <2 um diameter

2. Not myelinated

3. 1 m/sec

Lidocaine

impairs action potential propagation by blocking voltage-gated Na+ channels, uses as local anesthetic.

Tetrodotoxin (TTX)

a neurotoxin found in the internal organs of puffer fish. Selectively blocks nerve voltage-gated Na+ channels so then blocks AP generation and propagation. Very toxic, a single milligram or less is enough to kill an adult.

Continuous conduction

propagation of an AP along an unmyelinated axon

salutatory conduction

propagation of an AP along a myelinated axon