Effects of a protein phosphatase inhibitor, okadaic acid, on membrane currents of isolated guinea-pig cardiac myocytes

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Abstract
The effects of a protein phosphatase inhibitor, okadaic acid (OA), were studied on membrane currents of isolated myocytes from guinea-pig cardiac ventricle. The whole-cell Ca2+ current (I Ca) was recorded as peak inward current in response to test pulse to O mV. Extracellular application of OA (5–100μM) produced an increase ofI Ca. The effect was markedly enhanced when the myocyte was pretreated with threshold concentrations of isoprenaline.I Ca was increased from 11.3±0.8μA cm−2 to 19.0±1.1μA cm−2 (n=4) by 5μM-OA in the presence of 1nM-isoprenaline. The delayed rectifier current was also slightly increased. Furthermore, the wash-out time of the β-adrenergic increase ofI Ca was markedly prolonged by OA. The β-adrenergic stimulation of cardiac Ca2+ current is thought to be mediated by cAMP-dependent phosphorylation. The present results strongly suggest that the effect of OA onI Ca is related to inhibition of endogenous protein phosphatase activity which is responsible for the dephosphorylation process. By the isotope method, the inhibitory effect of OA on different types of phosphatase was compared. OA had a relatively high specificity to type 1-, and type 2A-phosphatases.