Critical contribution of KV1 channels to the regulation of coronary blood flow

Adam G. Goodwill, Jillian N. Noblet, Daniel Sassoon, Lijuan Fu, Ghassan S. Kassab, Luke Schepers, B. Herring, Trey S. Rottgen, Johnathan Tune, Gregory M. Dick

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Ion channels in smooth muscle control coronary vascular tone, but the identity of the potassium channels involved requires further investigation. The purpose of this study was to evaluate the functional role of KV1 channels on porcine coronary blood flow using the selective antagonist correolide. KV1 channel gene transcripts were found in porcine coronary arteries, with KCNA5 (encoding KV1.5) being most abundant (P < 0.001). Immunohistochemical staining demonstrated KV1.5 protein in the vascular smooth muscle layer of both porcine and human coronary arteries, including microvessels. Whole-cell patch-clamp experiments demonstrated significant correolide-sensitive (1–10 µM) current in coronary smooth muscle. In vivo studies included direct intracoronary infusion of vehicle or correolide into a pressure-clamped left anterior descending artery of healthy swine (n = 5 in each group) with simultaneous measurement of coronary blood flow. Intracoronary correolide (~0.3–3 µM targeted plasma concentration) had no effect on heart rate or systemic pressure, but reduced coronary blood flow in a dose-dependent manner (P < 0.05). Dobutamine (0.3–10 µg/kg/min) elicited coronary metabolic vasodilation and intracoronary correolide (3 µM) significantly reduced coronary blood flow at any given level of myocardial oxygen consumption (P < 0.001). Coronary artery occlusions (15 s) elicited reactive hyperemia and correolide (3 µM) reduced the flow volume repayment by approximately 30 % (P < 0.05). Taken together, these data support a major role for KV1 channels in modulating baseline coronary vascular tone and, perhaps, vasodilation in response to increased metabolism and transient ischemia.

Original languageEnglish (US)
Article number56
JournalBasic Research in Cardiology
Volume111
Issue number5
DOIs
StatePublished - Sep 1 2016

Fingerprint

Swine
Coronary Vessels
Vasodilation
Smooth Muscle
Blood Vessels
Pressure
Dobutamine
Coronary Occlusion
Potassium Channels
Hyperemia
Microvessels
Ion Channels
Vascular Smooth Muscle
Oxygen Consumption
correolide
Ischemia
Arteries
Heart Rate
Staining and Labeling
Genes

Keywords

  • Coronary circulation
  • Correolide
  • K1.5
  • KCNA5
  • Metabolic vasodilation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Goodwill, A. G., Noblet, J. N., Sassoon, D., Fu, L., Kassab, G. S., Schepers, L., ... Dick, G. M. (2016). Critical contribution of KV1 channels to the regulation of coronary blood flow. Basic Research in Cardiology, 111(5), [56]. https://doi.org/10.1007/s00395-016-0575-0

Critical contribution of KV1 channels to the regulation of coronary blood flow. / Goodwill, Adam G.; Noblet, Jillian N.; Sassoon, Daniel; Fu, Lijuan; Kassab, Ghassan S.; Schepers, Luke; Herring, B.; Rottgen, Trey S.; Tune, Johnathan; Dick, Gregory M.

In: Basic Research in Cardiology, Vol. 111, No. 5, 56, 01.09.2016.

Research output: Contribution to journalArticle

Goodwill, AG, Noblet, JN, Sassoon, D, Fu, L, Kassab, GS, Schepers, L, Herring, B, Rottgen, TS, Tune, J & Dick, GM 2016, 'Critical contribution of KV1 channels to the regulation of coronary blood flow', Basic Research in Cardiology, vol. 111, no. 5, 56. https://doi.org/10.1007/s00395-016-0575-0
Goodwill, Adam G. ; Noblet, Jillian N. ; Sassoon, Daniel ; Fu, Lijuan ; Kassab, Ghassan S. ; Schepers, Luke ; Herring, B. ; Rottgen, Trey S. ; Tune, Johnathan ; Dick, Gregory M. / Critical contribution of KV1 channels to the regulation of coronary blood flow. In: Basic Research in Cardiology. 2016 ; Vol. 111, No. 5.
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