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Journal of Neuroscience, Vol 7, 882-893, Copyright © 1987 by Society for Neuroscience
Blockade of Ca2+ and K+ currents in bag cell neurons of Aplysia californica by dihydropyridine Ca2+ antagonists
JM Nerbonne and AM Gurney
The effects of dihydropyridine calcium antagonists on whole-cell Ca2+ and
K+ currents in the neurosecretory bag cells of the marine mollusc Aplysia
californica have been investigated. Nifedipine and nisoldipine blocked bag
cell Ca2+ currents with effects similar to those seen previously on Ca2+
currents in cardiac muscle: both compounds appeared to interact with Ca2+
channels when they were closed, open, and inactivated. Also, as seen in
cardiac cells, nifedipine apparently binds with higher affinity to Ca2+
channels when they are inactivated than when they are either closed or
open. Nifedipine and nisoldipine also inhibited 2 outward K+ currents in
bag cells: the "delayed rectifier" (IK) and the "A" (IA) currents.
Half-maximal blockade of Ca2+ currents occurred at approximately 1.4 microM
nifedipine, compared to approximately 3-5 microM for half-maximal blockade
of IK and IA. The effects of these compounds on bag cell Ca2+ and K+
currents are interpreted and discussed here in terms of the "modulated
receptor" model of drug action. In contrast, however, no measurable effects
of nifedipine or nisoldipine were seen on Ca2+ (and/or K+) currents in
several vertebrate neuronal cell types. Our results suggest that there are
likely to be structural and/or conformational variations in Ca2+ channels
in different cells, tissues, and/or species and also that, in some cells,
Ca2+ and K+ channels might be structurally similar. These findings also
suggest, therefore, that if dihydropyridine binding is used to identify
Ca2+ channels, care should be taken to ensure that binding correlates
closely with the Ca2+ channels of interest.
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