Calcium channel function and regulation in β1- and β2-adrenoceptor transgenic mice.

Cardiac effects of catecholamines on the L-type calcium channel depend on β-adrenoceptor subtype (β₁- vs. β₂-adrenoceptor). Chronic overexpression of these receptors leads to hypertrophy and early death at moderate (β₁) or excessive (β₂) levels of overexpression respectively. In order to examine the role of L-type calcium channels in altered cardiomyocyte calcium homeostasis found with β₁-adrenoceptor overexpression, and to understand the quantitative differences between β-adrenoceptor subtypes regarding calcium channel regulation, we examined single channels in myocytes obtained from β₁- and β₂-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 β₁-adrenoceptor transgenic mice have normal baseline activity, and channel number is not reduced. This contrasts to previous findings with β₂-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 β₁-adrenoceptor transgenic myocytes. Furthermore, chronic β₁-adrenoceptor overexpression does not depress channel activity, giving another example of the difference between β₁- and β₂-adrenoceptor signal transduction. [ABSTRACT FROM AUTHOR]