Effects of inhibition of calcium and potassium currents in guinea-pig cardiac contraction:: comparison of β-caryophyllene oxide, eugenol, and nifedipine

1 To investigate the effects of the clove oil constituents P-caryophyllene oxide and eugenol on the heart muscle, experiments were performed on isolated papillary muscles and on ventricular myocytes of the guinea-pig. The results were compared with those obtained with the dihydropyridine, nifedipine. 2 All three substances exerted negative inotropic effects in heart muscle although with different potencies and different influences on the time course of the contraction curve. 3 They all reduced rested-state contractions (RSCs) in the presence of isoprenaline which are thought to be due to the Ca2+ current (I-Ca). 4 beta -Caryophyllene oxide, eugenol and nifedipine inhibited the I-Ca in single cells from the guineapig ventricle in a concentration-dependent, reversible way, but with different potencies. 5 In addition to the I-Ca-inhibiting effect, beta -caryophyllene oxide strongly inhibited and eugenol slightly inhibited the potassium current. 6 The action potential of papillary muscles at a 1 Hz contraction frequency was greatly shortened by nifedipine, slightly shortened by eugenol, but not changed by beta -caryophyllene oxide. 7 The inhibition of the potassium current by beta -caryophyllene oxide obviously prevents a shortening of the action potential due to the diminution of the I-Ca. Accordingly, the negative inotropic effect of beta -caryophyllene oxide is closely related to the inhibition of I-Ca. In contrast, eugenol and nifedipine, which shorten the action potential, exert stronger negative inotropic effects than expected from their influence on I-Ca. 8 The results show that the negative inotropic effect of a calcium channel blocker can be attenuated by an additional inhibition of potassium channels.