Regulation of the cardiac L-type calcium channel in L6 cells by arginine-vasopressin.
L-type Ca2+ channel activity was measured in L6 cells as nifedipine-sensitive barium (Ba2+; 5 mM) influx in a depolarizing salt solution containing 140 mM KCl. Addition of AVP (arginine-vasopressin) during Ba2+ uptake reduced the rate of Ba2+ influx by 60-100%; this was followed by a gradual restoration of the initial rate of Ba2+ uptake. Blockade of PKC (protein kinase C) by pretreatment with 10 muM bisindolylmaleimide did not affect the initial inhibition of Ba2+ influx, but completely abolished the recovery phase. The effect of AVP was half-maximal at 10 nM AVP and was blocked by the V1a receptor antagonist d-(CH2)(5)-Tyr(Me)-AVP. Activation of G(alphas) by isoprenaline or cholera toxin antagonized the actions of AVP on Ba2+ uptake. This protection persisted in the presence of the PKA (protein kinase A) inhibitor KT5720, and was not mimicked by agents that increase cAMP. Inhibition of Ba2+ influx was also elicited by ATP and ET (endothelin 1) with an order of effectiveness ET<ATP<AVP. Each of these agents has been reported to act through G(q)-coupled receptors. We conclude that activation of G(q)-coupled receptors produces a rapid inhibition of the cardiac L-type Ca2+ channel, which is subsequently overcome by activation of PKC.
Hantash
Basil M
BM
Department of Pharmacology and Physiology, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA. bhantash@stanford.edu
Thomas
Andrew P
AP
Reeves
John P
JP
D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001464:Barium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002227:Carbazoles; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019332:Endothelin-1; D004963:Estrenes; D019204:GTP-Binding Proteins / Q000378:metabolism; D007211:Indoles; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011758:Pyrroles; D011760:Pyrrolidinones; D051381:Rats
D020746:Calcium Channels, L-Type; D002227:Carbazoles; D019332:Endothelin-1; D004963:Estrenes; D007211:Indoles; D011758:Pyrroles; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D001127:Arginine Vasopressin; D001464:Barium; C057416:KT 5720; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases