Intro | Depolarization | Hyperpolarization | Action Potential | Threshold of Excitation
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The falling (or repolarization) phase of the action potential is dependent on the opening of potassium channels. At the peak of depolarization, the sodium channels close and potassium channels open. Potassium leaves the neuron with the concentration gradient and electrostatic pressure. Potassium channels remain open for a brief period of time beyond that necessary to return to the resting state of polarization. The extra efflux of potassium ions from the neuron results in a brief (approximately 1 millisecond) period of Hyperpolarization. During this period of hyperpolarization, another action potential cannot be triggered. The rate law of action potentials indicates that communication within the nervous system occurs via the timing or frequency of discharges and duration of pauses. The duration of hyperpolarization is the limiting factor in the rate at which action potentials can be initiated. This duration of approximately 1 millisecond means that the fastest rate for propagation of an impulse along an axon is approximately 1,000 per second.
Synthetic and natural molecules may affect different phases of the action potential, and thereby, affect the transmission of discharges. For example, scorpion venom acts to keep the sodium channels open and the potassium channels closed. This results in a prolonged state of depolarization. Local anesthetics such as Novocain and Xylocaine attach to the sodium channels, and thus prevent the flow of sodium into the cell. The net result is the blockage of neuronal stimulation. General anesthetics such as ether and chloroform function in a different fashion. These drugs decrease brain activity by opening K+ channels; thus allowing these ions out of the cell. The neuron becomes hyperpolarized, and is unable to discharge.
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The venom of some species of snakes and scorpions are toxic to the nervous system. Neurobiologists have spent considerable energy studying the neurotoxic effects of many of these substances, and this line of research has added much to our knowledge of neurophysiological mechanisms (Adams & Olivera, 1994; Mebs, 1989). Neurotoxins are proteins and peptides molecules that interact with membrane ion channels and receptors. Some scorpion neurotoxins modulate sodium ion channels (Possani LD, Becerril B, Delepierre M, Tytgat J, 1999); alpha toxins affect the mechanism of inactivation for these channels, while beta toxins affect the activation mechanism. Other neurotoxins modulate specifically potassium channels (Sorensen, Schneider, Rogowski & Blaustein, 1990). They may alter the frequency and duration of action potentials, the secretion of neurohormones, and neuromuscular function. The potassium channel neurotoxins inhibit a variety of channels that are based on the role calcium plays in the transport mechanism. In general, neurotoxin activity leads to changes in a neuron's discharge rate. Action potentials may be prolonged or the rate of discharge initiation increased. Sodium and calcium ions often accumulate in the neuron, with a resulting massive release of neurotransmitters. Much research has focused on defining the molecular structure of each toxin and its biological mechanism of action (Tsetlin, 1999). With this knowledge, peptides designed to modulate specific types of channels and receptor activities may be developed and used experimentally to expand our knowledge of neurophysiology.
| References |
Adams, M.E. & Olivera, B.M. (1994). Neurotoxins: overview of an emerging research technology. Trends in Neuroscience, 17(4), 151-155.
Mebs, D. (1989). Snake venoms: toolbox of the neurobiologist. Endeavour, 13(4), 157-161.
Possani, L.D., Becerril, B., Delepierre, M. & Tytgat J (1999). Scorpion toxins specific for Na+-channels. European Journal of Biochemistry, 264(2), 287-300.
Sorensen, R.G., Schneider, M.J., Rogowski, R.S. & Blaustein, M.P. (1990). Snake and scorpion neurotoxins as probes of rat brain synaptosomal potassium channels. Progress in Clinical Biological Research, 334, 279-301.
Tsetlin, V. (1999). Snake venom alpha-neurotoxins and other 'three-finger' proteins. European Journal of Biochemistry, 264(2), 281-286.