CONDUCTION OF ACTION POTENTIALS

1.         A neuron is usually stimulated at the dendrites or cell body and the resulting action potential then travels along the axon in one direction to the other end of the cell.

2.         Role of Dendrites in Transmission of Impulses

a.         The dendrites of the anterior motor neurons extend for 500 to 1000 microns in all directions from the neuronal soma.

b.            Therefore, these dendrites can receive signals from a large spatial area around the motor neuron – this provides vast opportunities for the summation of signals from many separate presynaptic nerves.

c.            Between 80 and 95 per cent of all the presynaptic terminals terminate on the dendrites of the anterior motor neuron – the preponderant share of the excitation of neurons is provided by signals transmitted by way of the dendrites.

d.            Transmission of Signals by Electrotonic Conduction:

i.          many dendrites fail to transmit action potentials because their membranes have few voltage-gated sodium channels.

ii.          they transmit electrotonic current down the dendrites to the soma by electrical conduction in the fluids of the dendrites with no generation of action potentials.

iii.         this current diminishes in strength as it reaches the soma due to loss of K ions and entry of CL ions through the membrane leak channels.

iv.         the decrease in membrane potential as it spreads electrotonically along dendrites toward the soma is called decremental conduction.

e.         If the electrotonic current that reaches the axon hillock is greater than the threshold, an action potential will be generated.

f.            Presence of Inhibitory Synapses:

i.          on the dendrite nearer to the soma.

ii.          on the axon hillock  

3.            Propagation of Action Potentials

a.         A graded potential at or above threshold reaches the trigger zone.

b.         The depolarization by the graded potential opens voltage-gated Na⁺ channels and Na⁺ enters the axon, moving down its electrochemical gradient.

c.         The influx of Na⁺ opens more Na⁺ channels; this process continues until all the Na⁺ channels are opened.

d.         The positive Na⁺ from the trigger zone moves into adjacent actions of the axon by local current flow.

e.         The next section of membrane becomes depolarized, opening Na⁺ channels in that region of the axon.

f.          Some current flows back into the cell body but has no effect because the cell body does not have voltage-gated channels.

g.         In the trigger zone, K⁺ gates have opened and Na⁺ gates have closed and K⁺ ions move out of the axon, repolarizing the membrane.

h.         The next section of the axon is in the rising phase of the action potential as Na⁺ flows into the cell and once again, positive charge flows to adjacent sections of the axon by local current flow.

i.          The backward movement of positive charge toward the cell body has no effect because the Na⁺ channels are inactivated – this is the refractory period.

j.          The depolarization opens Na⁺ channels and the action potential begins at that potential.

k.         Hence, the action potential moves down the axon in one direction by depolarizing adjacent areas of the axon until it reaches the axon terminal or synaptic knobs.

4.         Signal Transmission in Nerve Trunks

a.         Large axons are usually surrounded by a myelin sheath that is thicker than the axon and is interrupted once every 1 to 3mm along the axon’s length by a node of Ranvier.

b.         The multiple layers of membrane in myelin create a high-resistance sheath that prevents current flow between the cytoplasm of the neuron and the extracellular fluid.

c.         The node of Ranvier is a break in the continuity of the myelin sheath where the axoplasm is in direct contact with the extracellular fluid.

d.         When an action potential starts at the trigger zone, current flows rapidly down the myelinated axon to the first unmyelinated node of Ranvier.

e.         Each node has a high concentration of voltage-gated ion channels.

f.          When depolariztion reaches the node, Na⁺ channels open and Na⁺ enters the axon.

g.         The entry of Na⁺ depolarizes the adjacent section of the axon, causing a local current to flow to the next node.

h.         This apparent leapfrogging of the action potential from node to node is called saltatory conduction.

5.            Importance of Saltatory Conduction

a.         It increases the velocity of nerve transmission by causing depolarization process to jump long intervals from successive nodes along the axis of the nerve fiber:

i.          speed of conduction of unmyelinated axon: 0.5m/s.

ii.          speed of conduction in myelinated axon: 100m/s.

b.         It conserves energy for the axon as only the nodes polarize; the smaller loss of ions require little extra metabolism for re-establishing the Na⁺ - K⁺ gradient.

6.            Demyelinating diseases

a.         This is due to the loss of the myelin sheath from the neuron.

b.         In the central and peripheral nervous systems, the loss of myelin slows the conduction of action potentials.

c.         The strength of the action potentials decreases when current leaks out of the uninsulated regions of the membrane between the channel-rich nodes of Ranvier.

d.            Multiple sclerosis is well-known demyelinating disease characterized by fatigue, muscle weakness, difficulty in walking and loss of vision.

7.         Action potentials are conducted undiminished along the axon; this is due to a few factors:

a.         the intracellular fluid of the axon is a highy conductive electrolytic solution which offers little resistance to the conduction of electric current through it.

b.         the aggregation of Na⁺ channels at the nodes of Ranvier which open and replenish the depolarization because of Na⁺ influx – this maintains the original strength of the action potential.

c.         the insulating myelin sheath prevents the efflux of positive charges out of the axon and hence, the depolarization signal is not reduced in strength.

8.            Alteration of Electrical Activity in Neurons

a.         A large variety of chemicals alter the conduction of action potentials by binding to Na⁺ channels in the membrane of the axon:

i.            chemicals called neurotoxins bind to and inactivate Na⁺ channels; the venom of some snakes contains such neurotoxins that disrupts the flow of impulses.

ii.          local anesthetics like procaine and tetracaine act directly on the activation gates of the Na⁺ channels, inhibiting their opening.

iii.         If the Na⁺ channel is inactive, Na⁺ cannot enter the neuron.

iv.         Thus, a depolarization that begins at the trigger zone loses strength as it moves down the axon, much like a normal graded potential.

v.         If the wave of depolarization manages to reach the axon terminal, it is too weak to release the neurotransmitter and as a result, the message of the presynaptic neuron is not passed on to the postsynaptic cell.

b.         The concentration of K⁺ in the blood and interstitial fluid is the major determinant of the resting potential of all cells:

i.          an increase in blood K⁺ , hyperkalemia will shift the resting membrane potential of a neuron closer to threshold and cause cells to fire action potentials in response to smaller graded potentials.

ii.          this leads to weakness in contraction (due to increased in excitability of heart muscles) and eventual heart failure.

iii.         if the blood K⁺ levels drop too low, hypokalemia results: the resting membrane potential of the cells hyperpolarizes, moving farther from the threshold and requiring a larger than normal stimulus to fire an action potential.

iv.         this condition shows up as muscle weakness because the neurons are not firing normally.

c.         Effects of Acidosis:

i.          acidosis greatly depresses neuronal activity.

ii.          a fall in pH from 7.4 to below 7.0 usually causes a comatose state.

d.         Effects of Alkalosis:

i.            alkalosis greatly increases neuronal excitability.

ii.          an increase in arterial bloody pH from 7.4 to 7.8 often causes cerebral seizures because of increased excitability of the neurons.

e.         Effect of Hypoxia:

i.            neuronal excitability is highly dependent on an adequate supply of oxygen.

ii.            cessation of oxygen for only a few seconds can cause complete inexcitability of some neurons.

f.          Effects of Drugs:

i.            caffeine, theophylline and theobromine, which are found in coffee, tea, and cocoa respectively, all increase neuronal excitability of the neurons.

ii.            strychnine inhibits the action of inhibitory transmitters on the neurons, especially the effect of glycine in the spinal cord, causing the neurons to go into repetitive discharge, resulting in severe muscle spasms.

g.            Chemicals that affect Electrical Signals in Neurons:

9.            Fatigue of Synaptic Transmission

a.         When excitatory synapses are repetitively stimulated at a rapid rate, the number of discharges by the neuron increases and then becomes progressively less.

b.         This is called fatigue which operates in areas of overexcited nervous system, causing them to lose this excitability after a while.

c.         Causes of Fatigue:

i.            exhaustion of the stores of the transmitter substance in the postsynaptic membrane.

ii.            progressive inactivation of many of the postsynaptic membrane receptors.

iii.         the slow buildup of abnormal concentrations of ions inside the postsynaptic neuronal cell, which causes an inhibitory effect on the postsynaptic neuron.

10.       Post-Tetanic Facilitation

a.         When a rapidly repetitive series of impulses stimulates an excitatory synapse for a period of time and then a rest period is allowed, the synapse will often become for a period of seconds or minutes even more responsive to subsequent stimulation.

b.         This is caused mainly by the buildup of excess Ca²⁺ ions in the presynaptic terminals because the Ca² pump pumps too slowly to remove all of these immediately after each action potential.

c.         These accumulated Ca² ions cause more and more vesicular release of transmitter substance.

11.            Synaptic Delay

a.         In transmission of an action potential from a presynaptic neuron to a postsynaptic neuron, a certain amount of time is consumed in the process of:

i.            discharge of the transmitter substance by the presynaptic terminal.

ii.            diffusion of the transmitter to the membrane receptor.

iii.         action of the transmitter to increase the membrane permeability.

iv.         action of the receptor to increase the membrane permeability.

v.         inward diffusion of sodium.

b.         The minimal period of time required for all these events to take palce is 0.5ms.

c.            Neurophysiologist can measure the minimal delay time between an input volley of impulses and an output volley and from this can estimate the number of series of neurons in the circuit.