Modulation of K channels by coexpressed human alpha1C-adrenoceptor in Xenopus oocytes.
alpha1-Adrenoceptors participate in the regulation of inotropy and chronotropy in the heart. Modulation of cardiac K-channel function plays an important role in these alpha1-adrenergic functions. Studies of the mechanisms of K-channel modulation by alpha1-adrenoceptors are hampered by the coexistence of multiple receptor and channel subtypes in the heart. We therefore used a model system of coexpressing a specific receptor (human alpha1c-adrenoceptor) and a K-channel clone (hIsK, rKv1.2, or rKv1.4) in oocytes. alpha1c-Adrenoceptor stimulation caused a rapid upregulation of hIsK by elevating the intracellular Ca concentration. At least part of this effect was due to an activation of calmodulin and Ca/calmodulin-dependent protein kinase II. On the other hand, alpha1c-adrenoceptor stimulation caused a slow downregulation of rKv1.2 and rKvl.4 by activating protein kinase C. The differential modulation of K channels by alpha1c-adrenoceptors demonstrated in our experiments corroborates the complexity of alpha1-adrenergic functions in the heart. Our results indicate that the oocyte model system can be a useful approach in studying alpha1-adrenergic modulation of ion-channel function and signal transduction.
Tseng
G N
GN
Department of Pharmacology, Columbia University, New York, New York 10032, USA.
Yao
J A
JA
Tseng-Crank
J
J
D000818:Animals; D005260:Female; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D015221:Potassium Channels / Q000096:biosynthesis / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D014982:Xenopus laevis
D010703:Phorbol Esters; D015221:Potassium Channels; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D010656:Phenylephrine; C008876:phorbol-12,13-didecanoate; D013755:Tetradecanoylphorbol Acetate