Molecular aspects of adrenergic modulation of cardiac L-type Ca2+ channels.
L-type Ca(2+) channels are predominantly regulated by beta-adrenergic stimulation, enhancing L-type Ca(2+) current by increasing the mean channel open time and/or the opening probability of functional Ca(2+) channels. Stimulation of beta-adrenergic receptors (ARs) results in an increased cyclic adenosine monophosphate (cAMP) production by adenylate cyclase (AC) and consequently activation of protein kinase (PK) A and phosphorylation of L-type Ca(2+) channels by this enzyme. Beta(1)-Adrenergic receptors couple exclusively to the G protein Gs, producing a widespread increase in cAMP levels in the cell, whereas beta(2)-adrenergic receptors couple to both Gs and Gi, producing a more localized activation of L-type Ca(2+) channels. Other signaling intermediates (protein kinase C, protein kinase G or protein tyrosine kinase (PTK)) either have negative effects on L-type Ca(2+) current, or they interact with the stimulatory effect of the protein kinase A pathway.
van der Heyden
Marcel A G
MA
Department of Medical Physiology, University Medical Center Utrecht, P.O. Box 85060, 3508 AB Utrecht, The Netherlands. m.a.g.vanderheyden@med.uu.nl
Wijnhoven
Tessa J M
TJ
Opthof
Tobias
T
D018663:Adrenergic Agents / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D016415:Sequence Alignment
D018663:Adrenergic Agents; D020746:Calcium Channels, L-Type; D011941:Receptors, Adrenergic; D011494:Protein Kinases; D002118:Calcium