H2O2 activates redox- and 4-aminopyridine-sensitive Kv channels in coronary vascular smooth muscle.
Previously, we demonstrated that coronary vasodilation in response to hydrogen peroxide (H(2)O(2)) is attenuated by 4-aminopyridine (4-AP), an inhibitor of voltage-gated K(+) (K(V)) channels. Using whole cell patch-clamp techniques, we tested the hypothesis that H(2)O(2) increases K(+) current in coronary artery smooth muscle cells. H(2)O(2) increased K(+) current in a concentration-dependent manner (increases of 14 +/- 3 and 43 +/- 4% at 0 mV with 1 and 10 mM H(2)O(2), respectively). H(2)O(2) increased a conductance that was half-activated at -18 +/- 1 mV and half-inactivated at -36 +/- 2 mV. H(2)O(2) increased current amplitude; however, the voltages of half activation and inactivation were not altered. Dithiothreitol, a thiol reductant, reversed the effect of H(2)O(2) on K(+) current and significantly shifted the voltage of half-activation to -10 +/- 1 mV. N-ethylmaleimide, a thiol-alkylating agent, blocked the effect of H(2)O(2) to increase K(+) current. Neither tetraethylammonium (1 mM) nor iberiotoxin (100 nM), antagonists of Ca(2+)-activated K(+) channels, blocked the effect of H(2)O(2) to increase K(+) current. In contrast, 3 mM 4-AP completely blocked the effect of H(2)O(2) to increase K(+) current. These findings lead us to conclude that H(2)O(2) increases the activity of 4-AP-sensitive K(V) channels. Furthermore, our data support the idea that 4-AP-sensitive K(V) channels are redox sensitive and contribute to H(2)O(2)-induced coronary vasodilation.
Rogers
Paul A
PA
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Chilian
William M
WM
Bratz
Ian N
IN
Bryan
Robert M
RM
Dick
Gregory M
GM
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
D024642:Potassium Channels, Voltage-Gated; D019789:Tetraethylammonium; D006861:Hydrogen Peroxide; D015761:4-Aminopyridine