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Journal of Neuroscience, Vol 10, 2261-2267, Copyright © 1990 by Society for Neuroscience
Dihydropyridine actions on calcium currents of frog sympathetic neurons
SW Jones and LS Jacobs
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106.
Dihydropyridines (DHPs) generally have little effect on whole-cell calcium
currents of neurons, even at concentrations far higher than those effective
on muscle. Either neuronal calcium currents are much less sensitive to
DHPs, or only a small proportion of the current is DHP-sensitive. We find
that DHP agonists and antagonists act at low concentration on calcium
currents in frog sympathetic neurons but that the effects are small even at
optimal concentrations. The half-maximal dose (EC50) of the agonist Bay K
8644 is approximately 50 nM, and the effect of Bay K 8644 is blocked by 50%
at approximately 300 nM nifedipine, from a holding potential of -80 mV.
Nifedipine is more effective from a holding potential of -50 mV. These
results suggest the presence of an L-type calcium current, with DHP
sensitivity similar to L-currents in cardiac muscle. The predominant
(greater than 90%) calcium current in frog sympathetic neurons is a
DHP-resistant N-type current. However, high concentrations of DHPs (10
microM) partially block N-type calcium current, as well as
voltage-dependent sodium and potassium currents.
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