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Am J Physiol Heart Circ Physiol 279: H992-H999, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 3, H992-H999, September 2000

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

Jiqing Guo1, Wayne R. Giles1, and Christopher A. Ward2

1 Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1; and 2 Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6

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 (ICa,L) from -384 ± 77 to -439 ± 84 pA (116 ± 2%, n = 6). Additionally, the persistent or non-inactivating component of ICa,L was increased from -52 ± 3 to -88 ± 14 pA (174 ± 19%, n = 6). The hyperpolarization-activated current (If) 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 (IK) (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 ICa,L and that this effect is mediated by a PKC-dependent pathway.

patch clamp; action potential; potassium ion current; hyperpolarization-activated current; calcium ion current, sinoatrial nodal cells


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