Dihydropyridine Binding Sites Regulate Calcium Influx Through Specific Voltage‐Sensitive Calcium Channels in Cerebellar Granule Cells

Dihydropyridine Binding Sites Regulate Calcium Influx Through Specific Voltage‐Sensitive... Abstract: In primary cultures of cerebellar granule cells, (3H)nitrendipine binds with high affinity to a single site (KD 1 nM and Bmax 20 fmol/mg protein). The 1,4‐dihydropyridine (DHP) class of compounds such as nitrendipine, nifedipine, and BAY K 8644 displace (3H)nitrendipine binding at nanomolar concentrations. Verapamil partially inhibits whereas diltiazem slightly increases the (3H)nitrendipine binding. In these cells, the calcium influx that is induced by depolarization is very rapid and is blocked by micromolar concentrations of inorganic calcium blockers such as cadmium, cobalt, and manganese. The calcium influx resulting from cell depolarization is potentiated by BAY K 8644 and partially inhibited (approximately 40%) by nitrendipine and nifedipine. Other non‐DHP voltage‐sensitive calcium channel (VSCC) antagonists, such as verapamil and diltiazem, completely blocked the depolarization‐induced calcium influx. This suggested that nitrendipine and nifedipine block only a certain population of VSCCs. In contrast, verapamil and diltiazem do not appear to be selective and block all of VSCCs. Perhaps some VSCCs can be allosterically modulated by the binding site for the DHPs, whereas verapamil and diltiazem may block completely the function of all VSCCs by occupying a site that differs from the DHP binding site. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Dihydropyridine Binding Sites Regulate Calcium Influx Through Specific Voltage‐Sensitive Calcium Channels in Cerebellar Granule Cells

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Publisher
Wiley
Copyright
Copyright © 1988 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
DOI
10.1111/j.1471-4159.1988.tb10605.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: In primary cultures of cerebellar granule cells, (3H)nitrendipine binds with high affinity to a single site (KD 1 nM and Bmax 20 fmol/mg protein). The 1,4‐dihydropyridine (DHP) class of compounds such as nitrendipine, nifedipine, and BAY K 8644 displace (3H)nitrendipine binding at nanomolar concentrations. Verapamil partially inhibits whereas diltiazem slightly increases the (3H)nitrendipine binding. In these cells, the calcium influx that is induced by depolarization is very rapid and is blocked by micromolar concentrations of inorganic calcium blockers such as cadmium, cobalt, and manganese. The calcium influx resulting from cell depolarization is potentiated by BAY K 8644 and partially inhibited (approximately 40%) by nitrendipine and nifedipine. Other non‐DHP voltage‐sensitive calcium channel (VSCC) antagonists, such as verapamil and diltiazem, completely blocked the depolarization‐induced calcium influx. This suggested that nitrendipine and nifedipine block only a certain population of VSCCs. In contrast, verapamil and diltiazem do not appear to be selective and block all of VSCCs. Perhaps some VSCCs can be allosterically modulated by the binding site for the DHPs, whereas verapamil and diltiazem may block completely the function of all VSCCs by occupying a site that differs from the DHP binding site.

Journal

Journal of NeurochemistryWiley

Published: Apr 1, 1988

References

  • 45‐Ca ++ uptake into rat whole brain synaptosomes unaltered by dihydropyridine calcium antagonists
    Daniell, Daniell; Barr, Barr; Leslie, Leslie
  • Specific pharmacology of calcium in myocardium, cardiac pacemakers and vascular smooth muscle
    Fleckenstein, Fleckenstein
  • Bay K 8644, a 1,4‐dihydropyridine Ca 2+ channel activator: dissociation of binding and functional effects in brain synaptosomes
    Rampe, Rampe; Janis, Janis; Triggle, Triggle

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