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.
Foerster
Katharina
K
Department of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Kaeferstein
Tomas
T
Groner
Ferdi
F
Engelhardt
Stefan
S
Matthes
Jan
J
Koch
Walter J
WJ
Lohse
Martin J
MJ
Herzig
Stefan
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D017275:Isradipine / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol; D017275:Isradipine