AJP - Heart and Circulatory Physiology, Vol 258, Issue 6 1872-H1881, Copyright © 1990 by American Physiological Society

ARTICLES

Two pathways for Ca2+ channel gating differentially modulated by physiological stimuli

S. Richard, F. Tiaho, P. Charnet, J. Nargeot and J. M. Nerbonne
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.

In cardiac muscle, Ca2+ entry through voltage-gated Ca2+ channels plays an important role in the generation of action potentials and in the development of tension. Although it had been assumed that there was a single type of cardiac Ca2+ channel, recent studies reveal that multiple Ca2+ channel types coexist in some myocardial cells. Here, we report that macroscopic Ca2+ current (ICa) waveforms in isolated adult rat ventricular myocytes comprise two kinetically distinct components; these are referred to here as ICa (fc) and ICa (sc) to denote the fast and slow components, respectively, of ICa decay. In contrast to findings in other cells, the properties of ICa (fc) and ICa (sc) suggest the presence of two pathways for gating of a single type of high-threshold Ca2+ channel rather than two distinct Ca2+ channel types. In addition, gating via ICa (fc) and ICa (sc) is regulated by changes in membrane potential and stimulation frequency. Hyperpolarized potentials and low stimulation frequencies reveal preferential activation via ICa (fc); depolarized potentials and high stimulation frequencies, in contrast, favor activation via ICa (sc). After exposure to beta-adrenergic agonists or the Ca2+ agonist BAY K 8644, peak ICa amplitudes increase owing to the preferential augmentation of ICa (fc); beta-agonists and BAY K 8644 also increase ICa (sc), albeit to a smaller extent than ICa (fc). Thus, in addition to voltage- and frequency-dependent regulation, the two pathways for Ca2+ channel gating are modulated differentially by beta-adrenergic and Ca2+ channel agonists.

This article has been cited by other articles:

				P. J. F. Tucci, N. Murad, C. L. Rossi, R. J. Nogueira, and O. Santana Jr. Heart rate modulates the slow enhancement of contraction due to sudden left ventricular dilation Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2136 - H2143. [Abstract] [Full Text] [PDF]

				T. Cens, S. Restituito, A. Vallentin, and P. Charnet Promotion and Inhibition of L-type Ca2+ Channel Facilitation by Distinct Domains of the beta  Subunit J. Biol. Chem., July 17, 1998; 273(29): 18308 - 18315. [Abstract] [Full Text] [PDF]

				Z.-H. Zhang, J. A. Johnson, L. Chen, N. El-Sherif, D. Mochly-Rosen, and M. Boutjdir C2 Region–Derived Peptides of ß-Protein Kinase C Regulate Cardiac Ca2+ Channels Circ. Res., May 19, 1997; 80(5): 720 - 729. [Abstract] [Full Text]

				C. Piot, S. Lemaire, B. Albat, J. Seguin, J. Nargeot, and S. Richard High Frequency–Induced Upregulation of Human Cardiac Calcium Currents Circulation, January 1, 1996; 93(1): 120 - 128. [Abstract] [Full Text]

				R. Aggarwal and P. A. Boyden Diminished Ca2+ and Ba2+ Currents in Myocytes Surviving in the Epicardial Border Zone of the 5-Day Infarcted Canine Heart Circ. Res., December 1, 1995; 77(6): 1180 - 1191. [Abstract] [Full Text]