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The Journal of Neuroscience, August 15, 1998, 18(16):6113-6125
 -Latrotoxin Alters Spontaneous and Depolarization-Evoked
Quantal Release from Rat Adrenal Chromaffin Cells: Evidence for
Multiple Modes of Action
Jun
Liu and
Stanley
Misler
Departments of Medicine and Cell Biology/Physiology and Program in
Neuroscience, Washington University, St. Louis, Missouri 63110
 -Latrotoxin (-LT) potently enhances both
"spontaneous" and "depolarization-evoked" quantal
secretion from neurons. Here we have used the patch-clamped rat adrenal
chromaffin cell to examine simultaneously the effects of -LT on
membrane current or voltage, cytosolic Ca, and membrane capacitance,
the latter used as an assay for exocytosis. In chromaffin cells exposed
to toxin concentrations of >100 pM, the development of
large conductance, Ca-permeable ion channels, accompanied by a rise in
cytosolic Ca to levels near 1 µM, precedes the initiation
of spontaneous exocytosis. These channels appear to be induced
de novo, because they occur concurrently with
massive reduction or pharmacological block of voltage-dependent Na and
Ca currents. However, enhancement of depolarization-evoked release,
seen in many cells at <50 pM toxin, often occurs in the
absence of a rise in background cytosolic Ca or de novo
channel activity. These results favor Ca entry through toxin-induced
channels underlying initiation of spontaneous release and direct
modulation of the secretory machinery by the toxin-bound receptor
contributing to enhancement of depolarization-evoked secretion as well
as spontaneous release.
Key words:
neurotoxin; exocytosis; membrane capacitance; amperometry; cytosolic Ca; catecholamines
Copyright © 1998 Society for Neuroscience 0270-6474/98/18166113-13$05.00/0
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