Forskolin fails to activate L-type calcium current in hypertrophied cardiomyocytes of chronically hypoxic rats.
We have shown that the contractile, cytosolic calcium ([Ca2+]i) and cyclic AMP (cAMP) responses to beta-adrenoceptor stimulation are attenuated in ventricular myocytes of chronically hypoxic (CH) rats. The aim of this study was to examine the effect of forskolin on the L-type Ca2+ current in CH hypertrophied ventricular myocytes. Patch-clamp recording of the L-type Ca2+ current was measured in right ventricular myocytes of normoxic control and CH rats exposed to 10% inspired oxygen for 4 weeks. The breadth, but not the length, of CH myocytes was significantly greater than that of the control group. Activation of beta-adrenoceptor with isoproterenol (0.1 microM) increased the peak Ca2+ current by 83% in the normoxic control but the increase of peak Ca2+ current was not significant in the CH myocytes. Forskolin (0.1 - 1 microM), an activator of adenylyl cyclase, increased the peak Ca2+ current by 49% - 102% in the normoxic controls but it did not cause significant change of the peak Ca2+ current in CH myocytes. These results suggest an absence of forskolin-induced activation of Ca2+ current in hypertrophied ventricular myocytes during chronic hypoxia. The failure of activation of the Ca2+ current is consistent with the idea that adenylyl cyclase function is down-regulated in CH hypertrophied myocytes.
Fung
Man-Lung
ML
Department of Physiology, Institute of Cardiovascular Science and Medicine, University of Hong Kong, Pokfulam, People's Republic of China. fungml@hkucc.hku.hk
Li
Hung-Yu
HY
Wong
Tak-Ming
TM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005576:Colforsin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D005576:Colforsin; D000262:Adenylyl Cyclases