Electromechanical effects of okadaic acid isolated from black sponge in guinea‐pig ventricular muscles.

Abstract

Okadaic acid is a monocarboxylic acid with a unique molecular structure of C44H66O13. Okadaic acid, at concentrations above 10(‐5) M, caused a dose‐dependent increase of contractile force in guinea‐pig isolated ventricular muscles. The increase of contractile force by okadaic acid (1‐4 X 10(‐5) M) was accompanied by a prolongation of action potential duration (a.p.d.), while a.p.d. was shortened by okadaic acid at above 10(‐4) M. The okadaic‐acid‐induced changes in contractile force and a.p.d. were abolished by pre‐treatment with verapamil (2 X 10(‐6 M) or nifedipine (10(‐6) M). In a low‐Ca2+ medium (0.12 mM), the contractile response to okadaic acid (4 X 10(‐5) M) was inhibited, whereas the a.p.d. was more prolonged by the drug than in a control medium (containing 1.2 mM‐Ca2+). In a low‐Na+ (70 mM) medium or in a low‐Na+ (70 mM) and low‐Ca2+ (0.12 mM) medium both the contractile force and a.p.d. were unaffected by okadaic acid (4 X 10(‐5) M). The positive inotropic effect of okadaic acid (4 X 10(‐5) M) was not inhibited by treatment with tetrodotoxin (TTX, 2 X 10(‐6) M) or with ryanodine (2 X 10(‐6) M). In voltage‐clamp experiments using a single sucrose‐gap technique, okadaic acid (4 X 10(‐5) M), caused a significant increase of slow inward current, while it did not affect the net outward current. These findings suggest that okadaic acid has a positive inotropic effect on the heart, probably due to the enhancement of slow Ca2+ and/or Na+ inward current through the cell membrane. © 1986 The Physiological Society