2. Action Potentials

How does diameter and myelin affect action potential propagation?

1) conduction of an action potential along a nerve fibre is greatly enhanced by myelination. myelin acts to insulate the axon and the current flows almost totally at the nodes of ranvier. 2) axons with a large diameter have a lower internal resistance. as a result, conduction of an action potential is faster along axons with a larger diameter myelination contributes most to increasing conduction velocity (compared to diameter) in humans. Myelinated fibres are of greater diameter, but myelination makes a greater contribution to conduction velocity than does fibre diameter alone

What sequence of events must occur in order for an action potential to fire? Include threshold, and the opening and closing of Na+ and K+ channels.

1) stimulus gated ion channels open and the membrane depolarises slightly 2) membrane potential increases to -50mV 3) voltage gated Na+ channels open, increasing permeability to Na+ 4) voltage gated K+ channels open, increasing permeability to K+ 5) voltage gated Na+ channels close and deactivate 6) voltage gated K+ channels close 7) membrane potential returns to -70mV

Events in an action potential: 1

1. Initial depolarization starts when channels open in response to electrical, chemical, or mechanical stimulus. This allows local currents to flow. For the purpose of this lesson we will refer to these as stimulus-gated ion channels. As these channels open, there is a nonspecific increase in ion permeability. However, sodium ions are farthest from their electrochemical equilibrium (ENa) so they make the greatest contribution to the change in local current. As a result, there is some local membrane depolarization (that is, the membrane potential becomes slightly more positive). If the membrane potential reaches the threshold voltage (approximately -50mV), voltage-gated Na+ channels are activated and an action potential is initiated.

Events in an action potential: 2 depolarization

2. The opening of voltage-gated Na+ channels increases the membrane permeability to Na+. The membrane potential increases (becomes more positive) quickly moving towards the equilibrium potential for Na+ (ENa). This stage is called depolarization. Note that the peak of the action potential only reaches about +50 mV. This is because voltage-gated K+ channels are also activated by membrane depolarization during this time

Events in an action potential: 3 repolarization

3. Na+ channels close, but voltage-gated K+ channels remain open. The membrane potential falls back towards the resting membrane potential (becomes more negative). This stage is called repolarization

Events in an action potential: 4 hyperpolarization

4. The membrane potential continues to fall, and becomes more negative than the resting membrane potential. This stage is called hyperpolarization.

Events in an action potential: 5 RMP is restored

5. Voltage-gated K+ channels gradually close. As a consequence, the K+ permeability returns to its resting state as does the Na+ permeability. The Na+/K+-ATPase pump rapidly corrects for the tiny quantities of Na+ that were gained and K+ that were lost by pumping Na+ out of the cell and K+ into the cell, and RMP is restored.

Explain the resting membrane potential and how it is maintained

A resting (non-signaling) neuron has a voltage across its membrane called the resting membrane potential. The resting potential is determined by concentration gradients of ions across the membrane and by membrane permeability to each type of ion. In a resting neuron, there are concentration gradients across the membrane for Na+ and K+. Ions move down their gradients via channels, leading to a separation of charge that creates the resting potential. The membrane is much more permeable to K+ than to Na+ so the resting potential is close to the equilibrium potential of K+(the potential that would be generated by K+ if it were the only ion in the system).

Action potentials are "all or none"

Action potentials are "all or none" events. When an action potential begins, it propagates down the length of the axon. When the action potential reaches the end of the axon, a neurotransmitter is released into the synapse.

Resting membrane potential

All cells (including muscle cells and neurons) have a voltage difference across their cell membranes. This is the result of an uneven distribution of cations across the cell membrane, with potassium ions (K+) which are largely intracellular and sodium ions (Na+) which are largely extracellular. The cell uses energy from adenosine 5'-triphosphate (ATP) to power Na+/K+-ATPase pumps in the cell membrane. These pumps move three Na+ out of the cell, and two K+ into the cell with each cycle to maintain an uneven distribution of ions. The membrane is far more permeable to K+ than to Na+, so there is a greater tendency for K+ to diffuse out of the cell than for Na+ to diffuse into the cell. This results in the cell interior becoming negative compared to the cell exterior, and this potential difference is known as the resting membrane potential (RMP). The RMP of a healthy neuron is usually in the range of -70 to -80 mV. This potential difference across the membrane can be measured by inserting electrodes into the cell. In essence, we can regard the RMP as a diffusion potential dominated by the contribution of K+ diffusion.

What is an action potential?

An action potential is an event that is specific to excitable cells like neurons or muscle fibers. It involves a rapid and short-lasting rise in the electrical potential, immediately followed by a fall. This is the result of the opening and closing of channels in the membrane, which acutely change the membrane permeability to different ions. In nerves, action potentials start at the dendrites and are transmitted along the nerve axon. Therefore, action potentials transfer information over a distance.

Propagation of action potentials

At rest, the neuronal cell membrane is polarized with the inside negative relative to the outside. During an action potential, the polarity is briefly reversed. This change in polarity of the cell membrane produces local currents that cause depolarization of the cell membrane in the region of the action potential. When threshold is reached, voltage-gated Na+ channels open and an action potential is generated at the new location. Hence, action potentials self-propagate along an axon.

Factors that affect conduction velocity: Axon diameter

Axons with a larger diameter have a lower internal resistance. As a result, conduction of an action potential is faster along axons with larger diameter The survival advantage conveyed by the rapid conduction of action potentials is demonstrated by the numerous different animal groups that have evolved giant axons. The most famous of these are the giant axons of the squid, which may be up to 1 mm in diameter.

Does the concentration of sodium and potassium ions in the cell change much during an action potential?

Changes in membrane potential are a result of an increase in Na+ permeability, followed by an increase in K+ permeability. However only tiny amounts of these ions actually cross the membrane, so intracellular Na+ and K+ concentrations are not altered measurably by this. The idea of ions rushing in and out of the cells is a common misunderstanding about action potentials.

How nerves communicate - The Action Potential

Chemical synapses are the major way neurons modulate neuronal activity via excitation or inhibition of the postsynaptic neuron. They do this by altering the resting membrane potential. When they excite cells they bring the resting membrane potential (of around -65 mV) closer to 0 to cause and all or nothing event called the action potential.

How action potentials travel along myelinated fibers

Conduction of an action potential along a nerve fiber is greatly enhanced by myelin, which helps to insulate the axon and reduce loss of the electrical impulse. Sheaths of myelin that are about 20-300 layers thick surround the axon, and are separated every 1-2 mm by gaps called nodes of Ranvier. The presence of myelin decreases membrane capacitance and increases membrane resistance. The result is that much of that change in membrane permeability (and therefore current flow) occurs at the nodes. These nodes contain a high concentration of Na+ channels which allow for regeneration of the action potential as it travels along the axon. The action potential is described as "jumping" between the nodes of Ranvier; this process is called saltatory conduction

Diffusion potentials

Consider a simple system with a membrane permeable only to K+, separating two solutions which also contain Na+ and Cl- as shown on the right (values represent ion concentrations in mmol/L). Since the membrane is permeable only to K+, this ion can diffuse across the membrane. However, no other ions can move, even though the chemical potential gradients favor net Na+ movement and Cl- movements into the cell.

Absolute refractory period

During the absolute refractory period the membrane is completely resistant to further stimulation. This means that no matter how strongly the membrane is stimulated, another action potential will not fire. This is due to the characteristics of voltage-gated Na+ channels in the membrane. The "voltage-gated" property of these channels means that they are in different states (that is, open, closed, or inactivated) at different voltages. In the absolute refractory period a large number of these channels are voltage inactivated, and will only open again when the cell enters the relative refractory period

Relative refractory period

During the relative refractory period the membrane is more resistant to stimulation than usual. In this period some voltage-gated Na+ channels are still inactivated. As a result, a stronger stimulus than usual is required to open a sufficient number of these channels for another action potential to fire. The cell membrane is more permeable to K+ during this period. This further opposes depolarization of the membrane.

Explain Saltatory conduction

Electrical signals travel faster in axons that are insulated with myelin. Myelin, produced by glial support cells, wraps around axons and helps electrical current flow down the axon. Myelin insulation does not cover the entire axon, there are breaks in the wrapping. These breaks are called nodes of Ranvier. Action potentials traveling down the axon "jump" from node to node. This is called saltatory conduction . Saltatory conduction is a faster way to travel down an axon than traveling in an axon without myelin

refractory period

From the beginning of the action potential to the restoration of the RMP, the neuron is in a refractory period. This can be divided into two phases: In the absolute refractory period it is impossible to initiate a second action potential. In the relative refractory period a stimulus of greater than normal intensity can elicit a response.

Describe the absolute refractory period

The absolute refractory period refers to a period during the action potential. This is the time during which another stimulus given to the neuron (no matter how strong) will not lead to a second action potential. The absolute refractory period starts immediately after the initiation of the action potential and lasts until after the peak of the action potential. Following this period, the relative refractory period begins.

Factors that affect conduction velocity: Myelination

There are myelin producing cells in both the CNS and PNS Conduction of an action potential along a nerve fiber is greatly enhanced by myelination, which increases the resistance to current flow across the membrane. Sheaths of myelin are separated by gaps called nodes of Ranvier, which contain a high concentration of Na+ channels. As a result, current flow across the membrane occurs only at the nodes of Ranvier. Myelin accelerates nerve conduction velocity significantly and rates of 40-60 m/s (or even higher) can be found in human myelinated nerve fibers.

voltage-gated K+ channels

activation of these voltage-gated potassium channels is much slower than that of voltage-gated sodium channels. as a result, these potassium channels are referred to as 'delayed rectifiers' channels are activated to open by a threshold voltage of -40 to -50 mV. This is a similar voltage to that at which the voltage-gated Na+ channels open.

How does maintaining the resting membrane potential allow the continued firing of action potentials?

an action potential involves changes in membrane permeability to Na+ and K+, that occur as a result of different voltage gated channels opening and closing. these channels are activated and inactivated at specific voltages. therefore, restoring the resting membrane potential after an action potential is crucial for allowing these channels to function normally and so an action potential can fire

What is the physiological basis for the absolute and relative refractory periods?

during the absolute refractory period the membrane is completely resistant to further stimulation. this means that no matter how strongly the membrane is stimulated, another action potential will not fire. this is due to the characteristics of voltage gated Na+ channels in the membrane. the 'voltage gated' property of these channels means that they are in different states ( that is open/closed/inactivated) at different voltages. in the absolute refractory period, a large number of these channels are voltage INactivated, and will only open again when the cell enters the relative refractory period. during the relative refractory period, the membrane is more resistant to stimulation than usual. in this period some voltage gated Na+ channels are still inactivated. as a result, a stronger stimulus than usual is required to open a sufficient number of these channels for another action potential to occur. the cell membrane is more permeable to K+ during this period - further opposing depolarisation of the membrane

How do action potentials travel along a nerve fiber? Include an explanation of saltatory conduction.

in an unmyelinated axon, regeneration of the action potential occurs continuously along the axon. for myelinated axons, sheaths of myeline surround the axon and are separated by gaps called the nodes of Ranvier. the presence of myelin decreases membrane capacitance and increases membrane resistance. the result is that much of the change in membrane permeability (and therefore current flow) occurs at the nodes. these nodes contain a high concentration of Na+ channels which allow for regeneration of the action potential as it travels along the axons. the action potential is described as 'jumping' between the nodes of Ranvier - this process is called saltatory conduction

How does ion permeability change during depolarization, repolarization, and hyperpolarization?

in depolarisation, opening of voltage gated Na+ channels increases the membrane permeability to Na+. Voltage gated K+ channels are also active during this time, so the membrane is also permeable to K+ ions in repolarisation, Na+ channels close but voltage gated K+ channels are still open. membrane permeability to Na+ falls, but is still more permeable than normal to K+. this results in membrane hyperpolarization and the membrane potential returns to resting values only all of the voltage gated K+ channels close

What are the divisions of the nervous system and the general physiological roles of the nervous system? Include CNS and PNS, SNS and ANS.

the NS can be divided into two parts, the CNS and the PNS. the NS has three basic functions: 1) to sense changes within and external to the body 2) to process (integrate) this sensory information 3) to then initiate a response the PNS can be further divided into the SNS and ANS. the SNS is important for producing voluntary movement. in this system, information from the CNS travels directly to skeletal muscles along effector motor neurons. the ANS is important for involuntary movement and for controlling exocrine gland secretions. in this system, information from the CNS travels to smooth muscles, cardiac muscles and glands, along a two-neuron efferent pathway

Do action potentials in the body travel in one direction only, or in both? Explain your reasoning.

the absolute refractory period prevents backward propagation of an action potential. although it is possible for action potentials to experimentally pass either direction on the axon, normally APs arise at only one end of the nerve fiber. voltage gated Na+ channels enter a short-lived, inactive state after they have been open and this prevents the nerve from being re-excited (absolute refractory period!) . during this time the channel can not be reactivated by local currents.