|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 106, 175-201, Copyright © 1995 by The Rockefeller University Press
ARTICLES |
SP Kaspar and DJ Pelzer
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
The modulation of L-type Ca2+ current (ICa) by changes in stimulation frequency was investigated in single ventricular cardiomyocytes isolated from guinea pig hearts. Electrical recordings were carried out at 21-25 degrees C and at 33-37 degrees C with the whole-cell patch clamp method, under K(+)-free conditions. A comparison is made between the response to frequency changes for ICa in the basal state and after the application of drugs which elevate the level of adenosine-3',5'- cyclic monophosphate (cAMP) within the cells. Peak basal ICa was reduced with an increase in stimulation rate from 0.5 Hz to 1, 2, 3, 4, or 5 Hz. This frequency-induced reduction of ICa was enhanced by reduced temperature, was unchanged when Na+ or Ba2+ carried the basal Ca2+ channel current, and was greatly enhanced after elevating cAMP levels with forskolin, isoprenaline, or 8-(4-chlorophenylthio)-cyclic AMP. We examined the mechanism of the enhancement of the frequency- induced reduction of ICa by cAMP, and found two conditions which abolished it: (a) application of isoprenaline when Na+ carried the Ca2+ channel current in Ca(2+)-free solution, or (b) application of 3- isobutyl-1-methylxanthine, a broad-spectrum phosphodiesterase inhibitor. It was further shown that an elevation of both ICa and cAMP (induced by isoprenaline), and not an increase of ICa alone (induced by Bay K 8644), is required to produce the extra component of reduction by frequency. It is concluded that Ca2+ entry results in feedback regulation of ICa, through the activation of Ca(2+)-dependent phosphodiesterase(s). This is important in the context of sympathetic stimulation, which produces the companion conditions of an elevated heart rate and increases in cAMP levels and Ca2+ entry.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Pelzer, C. La, and D. J. Pelzer Phosphorylation-dependent modulation of cardiac calcium current by intracellular free magnesium Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1532 - H1544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 L. Kolby, P. Bernhardt, H. Ahlman, B. Wangberg, V. Johanson, A. Wigander, E. Forssell-Aronsson, S. Karlsson, B. Ahren, G. Stenman, et al. A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide Uptake Am. J. Pathol., February 1, 2001; 158(2): 745 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Bates and A. M. Gurney Use-dependent facilitation and depression of L-type Ca2+ current in guinea-pig ventricular myocytes: modulation by Ca2+ and isoprenaline Cardiovasc Res, November 1, 1999; 44(2): 381 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R.W. Money-Kyrle, C. H. Davies, H. K. Ranu, P. O'Gara, N. Singh Kent, P. A. Poole-Wilson, and S. E. Harding The role of cAMP in the frequency-dependent changes in contraction of guinea-pig cardiomyocytes Cardiovasc Res, February 1, 1998; 37(2): 532 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
