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Science 1 January 1988:
Vol. 239. no. 4835, pp. 57 - 61
DOI: 10.1126/science.2447647
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Articles

Science, Vol 239, Issue 4835, 57-61
Copyright © 1988 by American Association for the Advancement of Science

articles

Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons

LD Hirning, AP Fox, EW McCleskey, BM Olivera, SA Thayer, RJ Miller, and RW Tsien

Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.

Multiple types of calcium channels have been found in neurons, but uncertainty remains about which ones are involved in stimulus-secretion coupling. Two types of calcium channels in rat sympathetic neurons were described, and their relative importance in controlling norepinephrine release was analyzed. N-type and L-type calcium channels differed in voltage dependence, unitary barium conductance, and pharmacology. Nitrendipine inhibited activity of L-type channels but not N-type channels. Potassium-evoked norepinephrine release was markedly reduced by cadmium and the conesnail peptide toxin omega-Conus geographus toxin VIA, agents that block both N- and L-type channels, but was little affected by nitrendipine at concentrations that strongly reduce calcium influx, as measured by fura-2. Thus N-type calcium channels play a dominant role in the depolarization-evoked release of norepinephrine.


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