The Journal of Neuroscience, May 15, 1999, 19(10):3711-3722
A Current Activated on Depletion of Intracellular
Ca2+ Stores Can Regulate Exocytosis in Adrenal Chromaffin
Cells
Alla F.
Fomina and
Martha C.
Nowycky
Department of Neurobiology and Anatomy, Medical College of
Pennsylvania Hahnemann University, Philadelphia, Pennsylvania 19129
Exocytosis in excitable cells is strongly coupled to
Ca2+ entry through voltage-gated channels but can be
evoked by activation of membrane receptors that release
Ca2+ from inositol 1,4,5-trisphosphate-sensitive
internal stores. In many cell types, depletion of
Ca2+ stores activates Ca2+ influx
across the plasma membrane, a process known as capacitative or
store-operated Ca2+ entry. This influx is mediated
by a number of voltage-independent, Ca2+-selective
currents. In addition to replenishing Ca2+ stores,
these currents are hypothesized to play an important role in
agonist-evoked secretion in nonexcitable cells, although this has not
been confirmed experimentally. The existence and physiological function
of such currents in excitable cells is not known. Using the capacitance
detection technique to monitor exocytosis, we provide direct
experimental evidence that a similar mechanism exists in bovine adrenal
chromaffin cells. Depletion of intracellular Ca2+
stores with thapsigargin, a SERCA pump inhibitor, or with BAPTA, an
exogenous Ca2+ chelator, activates a
small-amplitude, voltage-independent current that is carried by
Ca2+ and Na+ ions.
Ca2+ entry through this pathway is sufficient to
stimulate exocytosis at negative membrane potentials. In addition,
depolarization-evoked exocytosis is markedly facilitated on activation
of the current. These data suggest that excitable cells possess a
store-operated Ca2+ influx mechanism that may both
directly trigger exocytosis and modulate excitation-secretion coupling.
Key words:
exocytosis; calcium-secretion coupling; store-operated
current; capacitance detection; synaptic plasticity; chromaffin cell,
capacitative Ca2+ entry
Copyright © 1999 Society for Neuroscience 0270-6474/99/19103711-12$05.00/0
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