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Endocrinology Vol. 140, No. 7 3025-3033
Copyright © 1999 by The Endocrine Society


ARTICLES

{alpha}-Latrotoxin Stimulates Inward Current, Rise in Cytosolic Calcium Concentration, and Exocytosis in at Pituitary Gonadotropes1

Frederick W. Tse2 and Amy Tse2

Department of Pharmacology and Division of Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2H7

Address all correspondence and requests for reprints to: Dr. Frederick W. Tse, Department of Pharmacology, 9–70 Medical Science Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. E-mail: fred.tse{at}ualberta.ca

{alpha}-Latrotoxin (LTX) from the black widow spider venom, stimulates neurotransmitter release from neuronal cells via Ca2+-dependent as well as Ca2+-independent mechanisms. In some peptide-secreting endocrine cells, however, LTX stimulates hormone release mainly via a Ca2+-independent mechanism. Here we investigated the action of LTX in rat pituitary gonadotropes that secrete the peptide, LH. Using the patch-clamp technique in conjunction with the fluorescent Ca2+ indicator (indo-1) to simultaneously measure the cytosolic Ca2+ concentration ([Ca2+]i) and ionic current, we showed that LTX elicited bursts of inward current that were accompanied by [Ca2+]i elevations. In the presence of a physiological concentration of extracellular Ca2+, the unitary conductance of the LTX-induced current was about 300 pS, and only about 6.4% of the current was carried by Ca2+. The LTX-induced current was occasionally followed by intracellular Ca2+ release. At [Ca2+]i of 1 µM or more, exocytosis (detected by membrane capacitance measurement) was consistently triggered, and it was frequently followed by endocytosis. Thus, LTX triggers Ca2+-dependent exocytosis in gonadotropes via extracellular Ca2+ entry as well as intracellular Ca2+ release. In approximately 25% of the cells, LTX could also trigger a slow exocytosis in the absence of [Ca2+]i elevation. Therefore, LTX has both Ca2+-dependent and Ca2+-independent actions in gonadotropes.




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Copyright © 1999 by The Endocrine Society