Calcium channel function and regulation in beta 1- and beta 2-adrenoceptor transgenic mice.

Cardiac effects of catecholamines on the L-type calcium channel depend on beta-adrenoceptor subtype (beta(1)- vs. beta(2)-adrenoceptor). Chronic overexpression of these receptors leads to hypertrophy and early death at moderate (beta(1)) or excessive (beta(2)) levels of overexpression respectively. In order to examine the role of L-type calcium channels in altered cardiomyocyte calcium homeostasis found with beta(1)-adrenoceptor overexpression, and to understand the quantitative differences between beta-adrenoceptor subtypes regarding calcium channel regulation, we examined single channels in myocytes obtained from beta(1)- and beta(2)-adrenoceptor transgenic mice. The effects of the agonist isoproterenol were investigated and compared with acute receptor stimulation in the respective non-transgenic littermates. Channels from beta(1)-adrenoceptor transgenic mice have normal baseline activity, and channel number is not reduced. This contrasts to previous findings with beta(2)-adrenoceptor transgenic mice, where channel activity is depressed. Isoproterenol is unable to stimulate channel activity in both transgenic models. In conclusion, the L-type calcium channel is not likely to be involved in alterations of calcium handling of beta(1)-adrenoceptor transgenic myocytes. Furthermore, chronic beta(1)-adrenoceptor overexpression does not depress channel activity, giving another example of the difference between beta(1)- and beta(2)-adrenoceptor signal transduction.