In-vivo phosphorylation of the cardiac L-type calcium channel beta-subunit in response to catecholamines.
In canine myocardium, the beta-subunit of the L-type Ca2+ channel is phosphorylated by cAMP dependent protein kinase in vitro as well as in vivo (Haase et al. FEBS Lett 335: 217-222, 1993). We have assessed the identity of the beta-subunit as well as its in vivo phosphorylation in representative experimental groups of catecholamine-challenged canine hearts. Adrenergic stimulation by high doses of both noradrenaline and isoprenaline induced rapid (within 20 sec) and nearly complete phosphorylation of the Ca2+ channel beta-subunit. Phosphorylation in vivo was about 4-fold higher as compared to untreated controls. When related to catecholamine-depleted (reserpine-treated) hearts noradrenaline and isoprenaline increased the in vivo phosphorylation of the beta-subunit even 8-fold. This phosphorylation correlated positively with tissue levels of cAMP, endogenous particulated cAMP-dependent protein kinase (PKA) and the rate of contractile force development dP/dtmax. The results imply the involvement of a PKA-mediated phosphorylation of the Ca2+ channel beta-subunit in the adrenergic stimulation of intact canine myocardium.
Haase
H
H
Max Delbrück Center for Molecular Medicine, Cardiology Section, Berlin-Buch, Germany.
Bartel
S
S
Karczewski
P
P
Morano
I
I
Krause
E G
EG
D000818:Animals; D001345:Autoradiography; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010766:Phosphorylation; D011487:Protein Conformation; D012110:Reserpine / Q000494:pharmacology
D015220:Calcium Channels; D002395:Catecholamines; D012110:Reserpine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D009638:Norepinephrine