An electrophysiological study on the anti-ventricular arrhythmic effect of adenosine in the guinea pig / 生理学报

ABSTRACT

Using whole-cell patch clamp technique this study investigated the effects of adenosine (Ado) on action potential, L-type calcium current (I(Ca.L)), delayed afterdepolarizations (DADs), and transient inward current (I(ti)) induced by isoproterenol (Iso) in guinea pig isolated single ventricular myocytes. The results showed (1) Ado alone had no significant direct effects on action potential and I(Ca.L) in guinea pig ventricular myocytes at 20-100 micromol/L. However, Ado significantly attenuated the prolongation of action potential duration (APD) and the increase of the peak amplitude of I(Ca.L) induced by Iso. Iso (10 nmol/L) markedly increased APD(50) and APD(90) from 340+/-21 ms to 486+/-28 ms and from 361+/-17 ms to 501+/-29 ms, respectively (P<0.01), and increased the amplitude of I(Ca.L) from 6.53+/-1.4 pA/pF to 18.28+/-2.4 pA/pF (P<0.01). The peak potential of current-potential relationship shifted to the left. Ado (50 micromol/L) abbreviated APD(50), APD(90) to 403+/-19 ms and 419+/-26 ms (P<0.01), and decreased the peak amplitude of I(Ca.L) to 10.2+/-1.5 pA/pF (P<0.01 vs Iso), but did not change resting membrane potential (RMP), action potential amplitude (APA), and overshoot (OS). (2) Iso (30 nmol/L) reproducibly elicited DADs with 100% incidence of DADs under this condition. Ado (50 micromol/L) completely inhibited Iso from inducing DADs. Iso (30 nmol/L) elicited I(ti) with 2-second depolarizing voltage-clamp pulses rising to +20 mV from a holding potential of -40 mV, the incidence of I(ti) being 100%, and the I(ti) was suppressed in the presence of Ado (50 micromol/L) with the incidence of I(ti) decreased to 14.3% (P<0.05). These data indicate that Ado antagonizes the stimulatory effect of Iso, and that the antiarrhythmic mechanism of Ado preventing Iso-induced DADs is due to the inhibition of intracellular Ca(2+) overload through attenuating the prolongation of APD, the enhance of I(Ca.L) and I(ti).