부산대학교 도서관

The abundance of voltage-gated L-type Ca2+ channels is altered by β-adrenergic receptor (β-AR) stimulation and by an elevation of the intracellular Ca2+ concentration in cardiac myocytes. In whole animal, chronic β-AR stimulation or pacing heart results in various changes in the abundance of the channel, but it reduces the β-AR responsiveness of the L-type channel. Because β-AR stimulation facilitates the L-type calcium channels, it is difficult in the whole animal to study the effects of β-AR and Ca2+ influx on the upregulation of the L-type channel independently of each other, which makes the cultur of nonbeating adult myocytes an attractive model. We found that culturing quiescent adult rabbit ventricular myocytes with isoproterenol (ISO, 2 μM) for 72 h or more caused a significant increase in the expression of mRNA coding for the L-type channel α1C 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 μM ISO increased the current amplitude even in ISO-treated cells. The increase in the current density, induced by sustained β-AR stimulation, was blocked by a β-AR antagonist, propranolol (10 μM), but not by a Ca2+ antagonist, nitrendipine (10 μM). In addition, the effects were reproduced by forskolin (10 μM), but not by a Ca2+ agonist, Bay-K 8644 (2 μM). Taken together, these results suggest that sustained β-AR stimulation upregulates L-type channel expression, but does not alter the β-AR responsiveness of the channel in quiescent myocytes.