Topics and Speakers John D. Koester, PhD
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Synopsis
How do neurons work? In this lecture, Dr John D. Koester discusses the action potential—how it is generated and the diversity of ion channels involved. He also describes neurologial diseases that result from disorders of the action potential.
The action potential is an electrical discharge that travels through a neuron to send a message to another neuron. It is proportional to the strength of the message; therefore, the stronger the input, the higher the firing and frequency of the message. The action potential is generated by differences in polarization inside and outside the cell. When the cell is at rest, its inside is negatively polarized at -70mV by a specific gradient of sodium, chloride, and potassium ions. When there is input to the neuron, sodium ions from the outside environment rush into the cell, depolarizing or making the inside of the cell more positive. At the same time, potassium ions rush out of the cell, further depolarizing the inside of the cell. If the inside of the neuron becomes depolarized to +55mV, then an action potential is generated and the neuron will fire its message. However, if it does not reach this "threshold" it will not fire: It is an "all or nothing" response. In short, an action potential occurs when there is an exchange of ions with the neuron's environment.
An essential part of the action potential are the so-called voltage-gated ion channels, multi-unit proteins that contain pores that help establish the voltage gradient in the neuronal environment. Sodium and potassium ions flow through these pores thereby establishing (or not establishing) an action potential. It is important to remember that these channels are not responsible for the occurrence of an action potential; they are simply catalysts in the process—the driving force behind the flow of the ions is simply the electromotive force. Evolution has taken care of producing different types of ion channels. They differ in the nature of their permeability, their kinetics of gating, their voltage range of activation, and the physiological modulators of gating. How these different types of ion channels are encoded in the genome are discussed in detail.
Dr Koester concludes the lecture with channelopathies, the name given to neurological diseases where these voltage-gated channels become disordered. There are many ways in which these channels can cause problems: sporadic or inherited mutations like myotonias; autoimmune diseases; and an increase or decrease in the expression of normal channels. For instance, myotonia is characterized by excessive excitability of muscle, resulting in muscle stiffness. That is, the muscle contraction outlasts the signal from the motor neuron. In this case, the sodium channels do not inactivate normally, resulting in excessive action potentials being generated in the muscle. Yet Dr Koester ends the lecture on a positive note: there is research under way to produce drugs that specifically target defective channels.
