Receptor-mediated regulation of IsK, a very slowly activating, voltage-dependent K+ channel in Xenopus oocytes.
Expression of IsK in Xenopus oocytes has been obtained in 2 ways: (i) by injection of cardiac polyA+ RNA from neonatal mouse heart; (ii) by injection of a cRNA synthesized in vitro. It was observed that polyA+ RNA not only directs the expression of the IsK channel but also contains purinergic P2 and endothelin receptors. Stimulation of these receptors, that produce intracellular Ca2+ increase together with diacylglycerol production activating protein kinase C, increases IsK activity. The same type of results and the same conclusions were obtained by co-injecting cRNA's corresponding to the 5-HT2 receptor and the IsK channel into oocytes. This stimulatory effect was shown to be due to Ca2+ via a calmodulin-dependent kinase process. Conversely, activation of protein kinase C pathway alone by phorbol esters leads to inhibition of IsK activity.
Honore
E
E
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Sophia Antipolis, Valbonne, France.
Attali
B
B
Lesage
F
F
Barhanin
J
J
Lazdunski
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D017466:Receptors, Endothelin; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014158:Transcription, Genetic; D014982:Xenopus laevis
D002147:Calmodulin; D016232:Endothelins; D008565:Membrane Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D011983:Receptors, Purinergic; D011985:Receptors, Serotonin; D013449:Sulfonamides; C059983:potassium channel protein I(sk); D011061:Poly A; D012701:Serotonin; D015759:Ionomycin; D012313:RNA; C017967:W 7; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; D002118:Calcium