TY - JOUR
T1 - H2O2 activates redox- and 4-aminopyridine-sensitive Kv channels in coronary vascular smooth muscle
AU - Rogers, Paul A.
AU - Chilian, William M.
AU - Bratz, Ian N.
AU - Bryan, Robert M.
AU - Dick, Gregory M.
PY - 2007/3
Y1 - 2007/3
N2 - Previously, we demonstrated that coronary vasodilation in response to hydrogen peroxide (H2O2) is attenuated by 4-aminopyridine (4-AP), an inhibitor of voltage-gated K+ (KV) channels. Using whole cell patch-clamp techniques, we tested the hypothesis that H 2O2 increases K+ current in coronary artery smooth muscle cells. H2O2 increased K+ current in a concentration-dependent manner (increases of 14 ± 3 and 43 ± 4% at 0 mV with 1 and 10 mM H2O2, respectively). H 2O2 increased a conductance that was half-activated at -18 ± 1 mV and half-inactivated at -36 ± 2 mV. H2O 2 increased current amplitude; however, the voltages of half activation and inactivation were not altered. Dithiothreitol, a thiol reductant, reversed the effect of H2O2 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 2O2 to increase K+ current. Neither tetraethylammonium (1 mM) nor iberiotoxin (100 nM), antagonists of Ca 2+-activated K+ channels, blocked the effect of H 2O2 to increase K+ current. In contrast, 3 mM 4-AP completely blocked the effect of H2O2 to increase K+ current. These findings lead us to conclude that H 2O2 increases the activity of 4-AP-sensitive KV channels. Furthermore, our data support the idea that 4-AP-sensitive K V channels are redox sensitive and contribute to H2O 2-induced coronary vasodilation.
AB - Previously, we demonstrated that coronary vasodilation in response to hydrogen peroxide (H2O2) is attenuated by 4-aminopyridine (4-AP), an inhibitor of voltage-gated K+ (KV) channels. Using whole cell patch-clamp techniques, we tested the hypothesis that H 2O2 increases K+ current in coronary artery smooth muscle cells. H2O2 increased K+ current in a concentration-dependent manner (increases of 14 ± 3 and 43 ± 4% at 0 mV with 1 and 10 mM H2O2, respectively). H 2O2 increased a conductance that was half-activated at -18 ± 1 mV and half-inactivated at -36 ± 2 mV. H2O 2 increased current amplitude; however, the voltages of half activation and inactivation were not altered. Dithiothreitol, a thiol reductant, reversed the effect of H2O2 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 2O2 to increase K+ current. Neither tetraethylammonium (1 mM) nor iberiotoxin (100 nM), antagonists of Ca 2+-activated K+ channels, blocked the effect of H 2O2 to increase K+ current. In contrast, 3 mM 4-AP completely blocked the effect of H2O2 to increase K+ current. These findings lead us to conclude that H 2O2 increases the activity of 4-AP-sensitive KV channels. Furthermore, our data support the idea that 4-AP-sensitive K V channels are redox sensitive and contribute to H2O 2-induced coronary vasodilation.
KW - Coronary circulation
KW - Delayed-rectifier potassium channels
KW - Peroxides
KW - Reactive oxygen species
KW - Sulfhydryl compounds
UR - http://www.scopus.com/inward/record.url?scp=33847720297&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00696.2006
DO - 10.1152/ajpheart.00696.2006
M3 - Article
C2 - 17071731
AN - SCOPUS:33847720297
SN - 0363-6135
VL - 292
SP - H1404-H1411
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3
ER -