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Chapter 5: Mechanisms of Neurotransmitter Release

John H. Byrne, Ph.D., Department of Neurobiology and Anatomy, McGovern Medical School

Revised 19 May 2020


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Calcium is a key ion involved in the release of chemical transmitter substances. Bernard Katz and his colleagues tested this hypothesis using the skeletal nerve muscle synapse preparation. Electrodes were placed near the terminal to initiate an action potential in the terminal. The preparation was perfused with a solution totally free of calcium. In order to control the delivery of calcium, another microelectrode was filled with calcium. Since Ca2+ is positively charged, it can be delivered to the vicinity of the synaptic terminal by briefly closing a switch connected to a battery in such a way that the positive pole forces minute amounts of calcium out of the electrode. In the absence of Ca2+ ejection, stimulation of the motor neuron produced no EPSP.
Just before the presynaptic axon was stimulated a second time, the switch was briefly closed to eject a small amount of calcium in the vicinity of the presynaptic terminal. A normal EPSP was recorded.
If the calcium ejection occurs after the action potential, again there was no EPSP. So this experiment demonstrates that calcium must be present before or during the action potential and the presynaptic terminal. Based on this experiment and others like it, Katz and colleagues proposed the calcium hypothesis for chemical synaptic transmission.

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