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Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane.

Publication ,  Journal Article
Rogart, RB; deBruyn Kops, A; Dzau, VJ
Published in: Proc Natl Acad Sci U S A
October 1986

Various Ca-channel blockers differ in cardiovascular action despite common effects at the Ca channel. Many investigators have reported only a single high-affinity receptor for binding of [3H]nitrendipine, a dihydropyridine Ca-channel blocker. Its equilibrium dissociation constant (Kd) does not match the concentration of nitrendipine needed for a physiological effect on the mammalian cardiac Ca channel. The purpose of these studies was to clarify the existing discrepancy between pharmacological properties of nitrendipine receptors and the physiological effects of the dihydropyridine blockers. Of particular importance in this regard was to provide a pharmacological correlate for electrophysiological studies demonstrating multiple voltage-dependent conformational states of the Ca channel, which show differing affinities for the dihydropyridine Ca-channel blockers. By use of an improved ligand binding assay, our studies demonstrate both "high-affinity" and "low-affinity" [3H]nitrendipine receptors with Kd values corresponding well with observed physiologically effective nitrendipine concentrations. We detected two distinct populations of nitrendipine receptors in rat heart and bovine aortic membrane. A high-affinity Kd value of 0.2-0.3 nM was found, which seems to correspond to the physiologically functional state of the Ca channel in smooth muscle, since the Kd value is similar to the concentration at which nitrendipine inhibits contraction. However, in contrast to numerous other studies, we observed that the predominant component of [3H]nitrendipine binding (95-99%) had a low-affinity Kd value (235 nM). This putative low-affinity [3H]nitrendipine receptor may correspond to the physiologically functional state of the Ca channel in cardiac muscle.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 1986

Volume

83

Issue

19

Start / End Page

7452 / 7456

Location

United States

Related Subject Headings

  • Sarcolemma
  • Rats
  • Radioligand Assay
  • Nitrendipine
  • Myocardium
  • Muscle, Smooth, Vascular
  • Ion Channels
  • In Vitro Techniques
  • Cattle
  • Calcium
 

Citation

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Rogart, R. B., deBruyn Kops, A., & Dzau, V. J. (1986). Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane. Proc Natl Acad Sci U S A, 83(19), 7452–7456. https://doi.org/10.1073/pnas.83.19.7452
Rogart, R. B., A. deBruyn Kops, and V. J. Dzau. “Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane.Proc Natl Acad Sci U S A 83, no. 19 (October 1986): 7452–56. https://doi.org/10.1073/pnas.83.19.7452.
Rogart RB, deBruyn Kops A, Dzau VJ. Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7452–6.
Rogart, R. B., et al. “Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane.Proc Natl Acad Sci U S A, vol. 83, no. 19, Oct. 1986, pp. 7452–56. Pubmed, doi:10.1073/pnas.83.19.7452.
Rogart RB, deBruyn Kops A, Dzau VJ. Identification of two calcium channel receptor sites for [3H]nitrendipine in mammalian cardiac and smooth muscle membrane. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7452–7456.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 1986

Volume

83

Issue

19

Start / End Page

7452 / 7456

Location

United States

Related Subject Headings

  • Sarcolemma
  • Rats
  • Radioligand Assay
  • Nitrendipine
  • Myocardium
  • Muscle, Smooth, Vascular
  • Ion Channels
  • In Vitro Techniques
  • Cattle
  • Calcium