Cellular electrophysiological basis for oxygen radical-induced arrhythmias. A patch-clamp study in guinea pig ventricular myocytes.

Abstract

Exposure to an exogenous source of oxygen radicals may induce major electrophysiological alterations in isolated myocytes, which might be related to changes in specific ionic currents and in level of intracellular calcium. These alterations occur with a time course consistent with the rapid onset of ventricular arrhythmias in reperfused hearts.

The effect of oxygen free radicals on calcium current and dihydropyridine binding sites in guinea‐pig ventricular myocytes

“…DHF has been shown to cause specific electrophysiological alterations in isolated ventricular myocytes when applied intra-or extracellularly (Cerbai et al, 1991;Jabr & Cole, 1993;Mugelli et al, 1995). The electrophysiological alterations caused by DHF are prevented by scavengers such as SOD, CAT (Cerbai et al, 1991), or mercaptopropionylglycine (Jabr & Cole, 1993). We have previously documented that DHF causes a reduction in ICa,L amplitude; a similar effect has been shown for other OFR-generating systems (Shattock et al, 1990;Tarr & Valenzeno, 1991;Coetzee & Opie, 1992;Nakaya et al, 1992;Gill et al, 1995 Lew et al (1991) Figure 3a).…”

“…The initial phase is paralleled by a decrease in calcium current, suggesting that the two phenomena are associated. SOD and CAT are able to prevent the effects of OFRs on DHP binding sites and we have previously demonstrated that they also prevent the electrophysiological alterations caused by the same source of free radicals (Cerbai et al, 1991 Ptasienski et al (1985) who showed that the presence of either Mg2+ or Ca2+ in the binding reaction solution results in the disappearance of the lower affinity state and in the conversion to a single high affinity state. Furthermore, the Bma,, value is superimposable on that found in homogenates of rabbit ventricular myocytes (Lew et al, 1991) using the same ligand, which, in isolated myocytes obtained by collagenase treatment, detects only DHP binding sites localised on the sarcolemma (Feron et al, 1992).…”

“…Saturation experiments were analysed by using the LIGAND Computer program (Munson & Rodbard, 1980 lished (Cerbai et al, 1991) Effect of OFR on calcium current…”

“…the relevant reactive oxygen metabolites formed during the reperfusion of the ischaemic myocardium (Bolfi et al, 1988;Zweier et al, 1989). DHF has been shown to cause specific electrophysiological alterations in isolated ventricular myocytes when applied intra-or extracellularly (Cerbai et al, 1991;Jabr & Cole, 1993;Mugelli et al, 1995). The electrophysiological alterations caused by DHF are prevented by scavengers such as SOD, CAT (Cerbai et al, 1991), or mercaptopropionylglycine (Jabr & Cole, 1993).…”

“…A decrease in DHP binding sites has been consistently obtained in cardiac membranes exposed to oxidant stress (Kaneko et al, 1989b;Matucci et al, 1992 (Cerbai et al, 1991). Furthermore, we tried to correlate the time course of the effects of OFRs on DHP binding sites with those on calcium current.…”