Cardiovascular effects of lepadiformine, an alkaloid isolated from the ascidians Clavelina lepadiformis (Muller) and C-moluccensis (Sluiter)

The effects of lepadiformine, a natural marine alkaloid isolated from the a scidians Clavelina lepadifonllis (Muller) and C. moluccensis (Sluiter), wer e studied in vivo by arterial blood pressure (aBP) recordings and electroca rdiograms (ECG) in anaesthetised rats and in situ by peripheral vascular pr essure recordings on perfused rabbit ear. Transmembrane resting (RP) and ac tion (AP) potentials were also recorded by intracellular microelectrodes on electrically stimulated left ventricular papillary muscle and spontaneousl y beating atrium isolated from rat and frog hearts, respectively. Intraveno us injection of lepadiformine (6 mg/kg) produced marked bradycardia and a l engthening of ECG intervals as well as a transient decrease of aBP, which r apidly returned to normal. The decrease of aBP may have been related to a v asoconstrictor effect observed in the perfused ear experiment. Lepadiformin e did not alter RP, bur significantly lengthened the repolarising phase of AP in rat papillary muscle and frog atrium. Lepadiformine also mimicked the effect of Ba2+ (0.2 mM) on the rat AP repolarising phase. Moreover, the le ngthening of the AP in frog atrium induced by lepadiformine still developed after the delayed outward K+ current (I-K) was blocked by tetraethylammoni um (10 mM). These observations suggest that lepadiformine-induced lengtheni ng of AP duration was not due to a decrease of I-K, but may reasonably be a ttributed to a reduction of the inward rectifying K+ current (I-K1). This b lockade of I-K1 could account for the cardiovascular effects of lepadiformi ne in vivo and in vitro and suggests that lepadiformine: has antiarrhythmic properties. (C) 2001 Elsevier Science Ltd. AH rights reserved.