Effect of hydrogen peroxide on the membrane currents of sinoatrial node cells from rabbit heart

Abstract

The effects of H2O2 on pacemaker activity and underlying membrane currents were studied in isolated rabbit sinoatrial (SA) node cells using perforated patch current- and voltage-clamp methods. Short-term exposure (<10 min) of the nodal cells to H2O2 (200 μM) resulted in an initial shortening of spontaneous action potential cycle length (from 445 ± 60 to 398 ± 56 ms; P < 0.05) and a prolongation of action potential duration. H2O2(100 μM) significantly increased peak L-type Ca2+ current ( I Ca,L) from −384 ± 77 to −439 ± 84 pA (116 ± 2%, n = 6). Additionally, the persistent or non-inactivating component of I Ca,L was increased from −52 ± 3 to −88 ± 14 pA (174 ± 19%, n = 6). The hyperpolarization-activated current ( I f) was decreased from −228 ± 62 to −161 ± 72 pA after exposure to H2O2 ( n = 7). There were no changes in the delayed rectifier K+ current ( I K) ( n = 7). H2O2-induced Ca2+ currents were blocked by 2 μM nicardipine ( n = 6), 2 mM Ni2+ ( n = 2), and the protein kinase C (PKC) inhibitor bisindolylmaleimide (10−7 M; n = 4) but not by 20 μM tetrodotoxin. These results suggest that H2O2 can increase the spontaneous pacing rate in rabbit SA node cells by enhancing I Ca,L and that this effect is mediated by a PKC-dependent pathway.