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Journal of Neuroscience, Vol 14, 4007-4024, Copyright © 1994 by Society for Neuroscience
An FCCP-sensitive Ca2+ store in bullfrog sympathetic neurons and its participation in stimulus-evoked changes in [Ca2+]i
DD Friel and RW Tsien
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, California 94305-5426.
This study describes a Ca2+ store in fura-2-loaded bullfrog sympathetic
neurons that modulates [Ca2+]i responses elicited by either depolarization
or Ca2+ release from a caffeine- and ryanodine-sensitive store. This store
is insensitive to caffeine and ryanodine, but is sensitive to the
protonophore carbonyl cyanide p- trifluoromethoxyphenylhydrazone (FCCP).
The FCCP-sensitive store slows both the rise in [Ca2+]i during stimulation
(apparently by accumulating Ca2+ from the cytosol) and the recovery
following stimulation (by releasing the accumulated Ca2+ into the cytosol).
For a fixed level of depolarization, recovery is slowed to an extent that
depends on stimulus duration. [Ca2+]i imaging shows that these effects are
prominent in the soma but not in growth cones. Ca2+ uptake by the FCCP-
sensitive store appears to be strongly [Ca2+]i dependent, since it becomes
influential only when [Ca2+]i approaches approximately 500 nM. Therefore,
this store may specifically influence [Ca2+]i during moderate and strong
stimulation. The effect of the store on responses to depolarization can be
accounted for by a simple three-compartment scheme consisting of the
extracellular medium, the cytosol, and a single internal store with a
[Ca2+]i-dependent uptake mechanism resembling the mitochondrial Ca2+
uniporter. The store's effect on responses to caffeine-induced Ca2+ release
can be accounted for by including a second internal compartment to
represent the caffeine- sensitive store. While the identity of the
FCCP-sensitive store is unknown, its sensitivity to FCCP is consistent with
a mitochondrial pool. It is suggested that by modulating the temporal
properties of [Ca2+]i following stimulation, the FCCP-sensitive store may
influence the degree of activation of intracellular [Ca2+]i-dependent
processes.
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