|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 100, 847-865, Copyright © 1992 by The Rockefeller University Press
ARTICLES |
KB Walsh and KJ Long
Department of Pharmacology, University of South Carolina, School of Medicine, Columbia 29208.
The enzymes cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) regulate the activity of cardiac ion channel proteins. In this study the whole-cell arrangement of the patch clamp technique was used to examine the effect of NaI on PKA-stimulated Cl- and Ca2+ channels in isolated guinea pig ventricular myocytes. Cl- currents (ICl) activated either by the beta-adrenergic agonist isoproterenol or the membrane- soluble cAMP analogue, 8-chlorphenylthio (8-CPT) cAMP, were greatly reduced in amplitude after substitution of an external solution containing 140 mM NaCl with a solution containing 140 mM NaI. This reduction was accompanied by a shift of -7 mV in the reversal potential (Erev) for ICl and could be reversed upon return to the NaCl external solution. Inhibition of ICl by NaI occurred in a concentration- dependent manner and was more pronounced for inward ICl (IC50 = 19 mM at -60 mV) than for outward ICl (IC50 = 60 mM at +60 mV). In contrast to ICl activated by PKA, ICl activated by PKC was slightly augmented in the presence of NaI and the Erev was found to shift by -15 mV. Based on these data, the relative permeability of I- to Cl- (PI/PCl) for this channel was calculated to be 1.79. NaI produced no change in the amplitude of inward calcium currents (ICa) recorded under basal conditions, but strongly inhibited ICa augmented by isoproterenol and 8- CPT cAMP, and during dialysis of cells with the catalytic subunit of PKA (CS). The in vitro incorporation of [gamma-32P]ATP into histone IIA and Kemptide, measured in the presence of PKA and cAMP, was not significantly different in assay mixtures containing salts of Cl- and I- . However, the ability of isoproterenol to augment basal ICa in whole- cell experiments was attenuated when experiments were carried out entirely in NaI external solution. Thus, the reduction in ICl and ICa observed in this study may result from a direct effect of I- on the phosphorylation/dephosphorylation of cardiac ion channel proteins or associated regulatory proteins.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. B. Walsh and Q. Cheng Intracellular Ca2+ regulates responsiveness of cardiac L-type Ca2+ current to protein kinase A: role of calmodulin Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H186 - H194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B Walsh and G. E Parks Changes in cardiac myocyte morphology alter the properties of voltage-gated ion channels Cardiovasc Res, July 1, 2002; 55(1): 64 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sorota Insights into the structure, distribution and function of the cardiac chloride channels Cardiovasc Res, May 1, 1999; 42(2): 361 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. Boockfor, R. A. Morris, D. C. DeSimone, D. M. Hunt, and K. B. Walsh Sertoli cell expression of the cystic fibrosis transmembrane conductance regulator Am J Physiol Cell Physiol, April 1, 1998; 274(4): C922 - C930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Walsh and C. Wang Arylaminobenzoate Block of the Cardiac Cyclic AMP-Dependent Chloride Current Mol. Pharmacol., March 1, 1998; 53(3): 539 - 546. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. A. Lathrop, A. Varro, P. P. Nanasi, I. Bodi, E. Takyi, and C. Pankucsi Differences in the Effects of d- and dl-Sotalol on Isolated Human Ventricular Muscle: Electromechanical Activity After Beta-Adrenoceptor Stimulation Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1996; 1(1): 65 - 73. [Abstract] [PDF]
|
|
|
|
 |
|
 S. McCartney, B. M. Little, L. K. Langeberg, and J. D. Scott Cloning and Characterization of A-kinase Anchor Protein 100 (AKAP100) J. Biol. Chem., April 21, 1995; 270(16): 9327 - 9333. [Abstract] [Full Text] [PDF]
|
|
|
|
