Okadaic acid enhances prepulse facilitation of cardiac alpha 1-subunit but not endogenous calcium channel currents in Xenopus laevis oocytes.
Xenopus laevis oocytes can be selected to express relatively high levels of endogenous Ca currents. These currents are facilitated by prepulses. Facilitated endogenous Ca currents are unaffected by okadaic acid, RpcAMPS or the dihydropyridine (DHP) antagonist (+) PN 200-110. The endogenous currents and facilitation of endogenous currents by depolarizing prepulses are fully blocked by 1 mM Cd2+. In contrast, oocytes injected with mRNA encoding for the rabbit cardiac alpha 1-subunit express prepulse-facilitated Ca channel currents that are highly enhanced by the phosphoprotein phosphatase inhibitor okadaic acid (3-fold) and blocked by RpcAMPS and the DHP antagonist (+) PN 200-110. While okadaic acid selectively stimulates prepulse facilitation of cardiac alpha 1-subunit Ca currents, the DHP agonist (+) SDZ 202-791 largely increases (5-fold) both the control (before prepulse) and facilitated currents (after prepulse). (+) SDZ 202-791 did not prevent the effect of RpcAMPS or okadaic acid on facilitation of cardiac alpha 1-subunit, suggesting that DHP stimulation is independent of phosphorylation leading to channel facilitation. The enhancement of prepulse facilitation of cardiac alpha 1L-subunit Ca channel current by okadaic acid can be accounted for by a speeding up in the rates of onset during the prepulse. Inhibition of phosphoprotein phosphatases by okadaic acid has only modest effects on the rates of recovery of cardiac alpha 1-subunit Ca channel current from facilitation in the time immediately following the prepulse.
Chahine
M
M
Laval Hospital, Research Center, St-Foy, QC, Canada.
Bibikova
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Sculptoreanu
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D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D017275:Isradipine / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D014982:Xenopus laevis
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D019319:Okadaic Acid; D002122:Calcium Chloride; D017275:Isradipine