Voltage-dependent K+ channels regulate the duration of reactive hyperemia in the canine coronary circulation

Gregory M. Dick, Ian N. Bratz, Léna Borbouse, Gregory A. Payne, Ü Deniz Dincer, Jarrod D. Knudson, Paul A. Rogers, Johnathan D. Tune

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56 Scopus citations


We previously demonstrated a role for voltage-dependent K+ (KV) channels in coronary vasodilation elicited by myocardial metabolism and exogenous H2O2, as responses were attenuated by the KV channel blocker 4-aminopyridine (4-AP). Here we tested the hypothesis that KV channels participate in coronary reactive hyperemia and examined the role of KV channels in responses to nitric oxide (NO) and adenosine, two putative mediators. Reactive hyperemia (30-s occlusion) was measured in open-chest dogs before and during 4-AP treatment [intracoronary (ic), plasma concentration 0.3 mM]. 4-AP reduced baseline flow 34 ± 5% and inhibited hyperemic volume 32 ± 5%. Administration of 8-phenyltheophylline (8-PT; 0.3 mM ic or 5 mg/kg iv) or N G-nitro-L-arginine methyl ester (L-NAME; 1 mg/min ic) inhibited early and late portions of hyperemic flow, supporting roles for adenosine and NO. 4-AP further inhibited hyperemia in the presence of 8-PT or L-NAME. Adenosine-induced blood flow responses were attenuated by 4-AP (52 ± 6% block at 9 μg/min). Dilation of arterioles to adenosine was attenuated by 0.3 mM 4-AP and 1 μM correolide, a selective KV1 antagonist (76 ± 7% and 47 ± 2% block, respectively, at 1 μM). Dilation in response to sodium nitroprusside, an NO donor, was attenuated by 4-AP in vivo (41 ± 6% block at 10 μg/min) and by correolide in vitro (29 ± 4% block at 1 μM). KV current in smooth muscle cells was inhibited by 4-AP (IC50 1.1 ± 0.1 mM) and virtually eliminated by correolide. Expression of mRNA for KV1 family members was detected in coronary arteries. Our data indicate that KV channels play an important role in regulating resting coronary blood flow, determining duration of reactive hyperemia, and mediating adenosine- and NO-induced vasodilation.

Original languageEnglish
Pages (from-to)H2371-H2381
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5
StatePublished - May 2008


  • 4-aminopyridine
  • Adenosine
  • Delayed rectifier potassium channel
  • Ischemic vasodilation
  • Vascular smooth muscle


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