alpha-Latrotoxin alters spontaneous and depolarization-evoked quantal release from rat adrenal chromaffin cells: evidence for multiple modes of action.
alpha-Latrotoxin (alpha-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 alpha-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 microM, 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.
Departments of Medicine and Cell Biology/Physiology and Program in Neuroscience, Washington University, St. Louis, Missouri 63110, USA.
J
J
Liu
S
S
Misler
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D019439:Chromaffin Cells / Q000187:drug effects* / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D005089:Exocytosis / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*
D015220:Calcium Channels; D013111:Spider Venoms; C020763:alpha-latrotoxin; D002118:Calcium