Sustained beta-adrenergic stimulation increased L-type Ca2+ channel expression in cultured quiescent ventricular myocytes.
The abundance of voltage-gated L-type Ca2+ channels is altered by beta-adrenergic receptor (beta-AR) stimulation and by an elevation of the intracellular Ca2+ concentration in cardiac myocytes. In whole animal, chronic beta-AR stimulation or pacing heart results in various changes in the abundance of the channel, but it reduces the beta-AR responsiveness of the L-type channel. Because beta-AR stimulation facilitates the L-type calcium channels, it is difficult in the whole animal to study the effects of beta-AR and Ca2+ influx on the upregulation of the L-type channel independently of each other, which makes the culture of nonbeating adult myocytes an attractive model. We found that culturing quiescent adult rabbit ventricular myocytes with isoproterenol (ISO, 2 microM) for 72 h or more caused a significant increase in the expression of mRNA coding for the L-type channel alpha(1C) subunit by approximately twofold as compared to time-matched controls, and it was followed by a 1.8-fold increase in the Ca2+ current density at 96 h. Somewhat surprisingly, an acute application of 1 microM ISO increased the current amplitude even in ISO-treated cells. The increase in the current density, induced by sustained beta-AR stimulation, was blocked by a beta-AR antagonist, propranolol (10 microM), but not by a Ca2+ antagonist, nitrendipine (10 microM). In addition, the effects were reproduced by forskolin (10 microM), but not by a Ca2+ agonist, Bay-K 8644 (2 microM). Taken together, these results suggest that sustained beta-AR stimulation upregulates L-type channel expression, but does not alter the beta-AR responsiveness of the channel in quiescent myocytes.
Akuzawa-Tateyama
Miyuki
M
Department of Physiology, Juntendo University School of Medicine, Hongo, Tokyo, Japan.
Tateyama
Michihiro
M
Ochi
Rikuo
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009568:Nitrendipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D012333:RNA, Messenger; D009568:Nitrendipine; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium