PT - JOURNAL ARTICLE AU - Jun Liu AU - Stanley Misler TI - α-Latrotoxin Alters Spontaneous and Depolarization-Evoked Quantal Release from Rat Adrenal Chromaffin Cells: Evidence for Multiple Modes of Action AID - 10.1523/JNEUROSCI.18-16-06113.1998 DP - 1998 Aug 15 TA - The Journal of Neuroscience PG - 6113--6125 VI - 18 IP - 16 4099 - http://www.jneurosci.org/content/18/16/6113.short 4100 - http://www.jneurosci.org/content/18/16/6113.full SO - J. Neurosci.1998 Aug 15; 18 AB - α-Latrotoxin (α-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 α-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 inducedde 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 novochannel 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.