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 leve ls of endogenous Ca currents. These currents are facilitated by prepul ses. 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 depolar izing prepulses are fully blocked by 1 mM Cd2+. In contrast, oocytes i njected with mRNA encoding for the rabbit cardiac alpha(1)-subunit exp ress 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 okada ic acid selectively stimulates prepulse facilitation of cardiac alpha( 1)-subunit Ca currents, the DHP agonist (+) SDZ 202-791 largely increa ses (5-fold) both the control (before prepulse) and facilitated curren ts (after prepulse). (+) SDZ 202-791 did not prevent the effect of Rpc AMPS or okadaic acid on facilitation of cardiac alpha(1)-subunit, sugg esting that DHP stimulation is independent of phosphorylation leading to channel facilitation. The enhancement of prepulse facilitation of c ardiac alpha(1L)-subunit Ca channel current by okadaic acid can be acc ounted for by a speeding up in the rates of onset during the prepulse. Inhibition of phosphoprotein phosphatases by okadaic acid has only mo dest effects on the rates of recovery of cardiac alpha(1)-subunit Ca c hannel current from facilitation in the time immediately following the prepulse.