The release of neurotransmitters from presynaptic nerve terminals by the fusion of transmitter-filled secretory vesicles with the nerve terminal membrane is critical for the transfer of information throughout the nervous system. This release is gated by the influx of calcium ions via voltage-gated ion channels and the control of channel availability is a major mechanism in the control of synaptic strength, and hence, synaptic pathways. We are exploring the function of these calcium channels by several different approaches. First, the activation of other ion channel types that affect the excitability of the nerve terminal can be critical for the control of calcium channel activity. Key amongst these are the potassium channels which effectively clamp the nerve terminal to very negative potentials, preventing or inhibiting action potential invasion. We have tested for voltage sensitive potassium channels by immunocytochemical and biophysical approaches applied to the giant presynaptic terminal of the chick ciliary ganglion and have identified several members of the Kv class of channel in the nerve terminal. Second, we have continued our exploration of the relationship between these calcium channels and the transmitter release site by testing why cleavage of syntaxin, a transmitter release site associated protein, eliminates a main pathway of calcium channel modulation via G proteins. We find that syntaxin may play a role in localizing the G protein to the presynaptic calcium channel. Third, we have examined the mechanisms whereby calcium ions are extruded from the nerve terminal by localizing the calcium pumps and the sodium-calcium exchangers. Contrary to expectations, the exchangers are at locations that are distant from the transmitter release sites whereas the pumps are at the release sites themselves.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
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Bio-Organic and Natural Products Chemistry Study Section (BNP)
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