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. 1984 Aug;81(15):4824–4827. doi: 10.1073/pnas.81.15.4824

Dihydropyridine derivatives prolong the open state of Ca channels in cultured cardiac cells.

S Kokubun, H Reuter
PMCID: PMC391583  PMID: 6205402

Abstract

The dihydropyridine derivatives CGP 28392 and BAY K 8644 exert a strong positive inotropic effect in mammalian cardiac muscle, presumably by increasing Ca influx during the action potential. Analysis of the drug effects at the level of single Ca channels by means of the patch-clamp method revealed complicated changes in the kinetics of channel gating. The prevailing effect is a prolongation of the mean open time of Ca channels. In addition, the intervals between channel openings can be slightly prolonged. Ensemble averages of single-channel traces showed a concentration-dependent increase in the mean current amplitude by the drugs. In contrast to beta-adrenoceptor agonists, the increase in Ca current by the dihydropyridine derivatives is not associated with an increase in the intracellular cyclic AMP level.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bean B. P., Nowycky M. C., Tsien R. W. Beta-adrenergic modulation of calcium channels in frog ventricular heart cells. 1984 Jan 26-Feb 1Nature. 307(5949):371–375. doi: 10.1038/307371a0. [DOI] [PubMed] [Google Scholar]
  2. Bellemann P., Schade A., Towart R. Dihydropyridine receptor in rat brain labeled with [3H]nimodipine. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2356–2360. doi: 10.1073/pnas.80.8.2356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cachelin A. B., De Peyer J. E., Kokubun S., Reuter H. Sodium channels in cultured cardiac cells. J Physiol. 1983 Jul;340:389–401. doi: 10.1113/jphysiol.1983.sp014768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cachelin A. B., de Peyer J. E., Kokubun S., Reuter H. Ca2+ channel modulation by 8-bromocyclic AMP in cultured heart cells. Nature. 1983 Aug 4;304(5925):462–464. doi: 10.1038/304462a0. [DOI] [PubMed] [Google Scholar]
  5. Cavalié A., Ochi R., Pelzer D., Trautwein W. Elementary currents through Ca2+ channels in guinea pig myocytes. Pflugers Arch. 1983 Sep;398(4):284–297. doi: 10.1007/BF00657238. [DOI] [PubMed] [Google Scholar]
  6. Curtis B. M., Catterall W. A. Solubilization of the calcium antagonist receptor from rat brain. J Biol Chem. 1983 Jun 25;258(12):7280–7283. [PubMed] [Google Scholar]
  7. Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [DOI] [PubMed] [Google Scholar]
  8. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  9. Lee K. S., Tsien R. W. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983 Apr 28;302(5911):790–794. doi: 10.1038/302790a0. [DOI] [PubMed] [Google Scholar]
  10. Osterrieder W., Brum G., Hescheler J., Trautwein W., Flockerzi V., Hofmann F. Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. Nature. 1982 Aug 5;298(5874):576–578. doi: 10.1038/298576a0. [DOI] [PubMed] [Google Scholar]
  11. Porzig H., Becker C., Reuter H. Competitive and non-competitive interactions between specific ligands and beta-adrenoceptors in living cardiac cells. Naunyn Schmiedebergs Arch Pharmacol. 1982 Nov;321(2):89–99. doi: 10.1007/BF00518474. [DOI] [PubMed] [Google Scholar]
  12. Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
  13. Reuter H., Stevens C. F., Tsien R. W., Yellen G. Properties of single calcium channels in cardiac cell culture. Nature. 1982 Jun 10;297(5866):501–504. doi: 10.1038/297501a0. [DOI] [PubMed] [Google Scholar]
  14. Schramm M., Thomas G., Towart R., Franckowiak G. Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature. 1983 Jun 9;303(5917):535–537. doi: 10.1038/303535a0. [DOI] [PubMed] [Google Scholar]

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