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-Latrotoxin Stimulates Inward Current, Rise in Cytosolic Calcium Concentration, and Exocytosis in at Pituitary Gonadotropes1
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, 970 Medical Science Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. E-mail: fred.tse{at}ualberta.ca
-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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