Effect of hydrogen peroxide on the membrane currents of sinoatrial node cells from rabbit heart.
The effects of H(2)O(2) 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 H(2)O(2) (200 microM) 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. H(2)O(2) (100 microM) significantly increased peak L-type Ca(2+) 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 H(2)O(2) (n = 7). There were no changes in the delayed rectifier K(+) current (I(K)) (n = 7). H(2)O(2)-induced Ca(2+) currents were blocked by 2 microM nicardipine (n = 6), 2 mM Ni(2+) (n = 2), and the protein kinase C (PKC) inhibitor bisindolylmaleimide (10(-7) M; n = 4) but not by 20 microM tetrodotoxin. These results suggest that H(2)O(2) 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.
Guo
J
J
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1.
Giles
W R
WR
Ward
C A
CA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D011930:Reaction Time / Q000187:drug effects; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013779:Tetrodotoxin; D006861:Hydrogen Peroxide; D011493:Protein Kinase C