Contribution of KV7 Channels to Basal Coronary Flow and Active Response to Ischemia

TY - JOUR

T1 - Contribution of KV7 Channels to Basal Coronary Flow and Active Response to Ischemia

AU - Khanamiri, Saereh

AU - Soltysinska, Ewa

AU - Jepps, Thomas A

AU - Bentzen, Bo H

AU - Chadha, Preet S

AU - Schmitt, Nicole

AU - Greenwood, Iain A

AU - Olesen, Søren-Peter

PY - 2013/9/30

Y1 - 2013/9/30

N2 - The goal of the present study was to determine the role of KCNQ-encoded KV channels (KV7 channels) in the passive and active regulation of coronary flow in normotensive and hypertensive rats. In left anterior descending coronary arteries from normotensive rats, structurally different KV7.2 to 7.5 activators produced relaxations, which were considerably less in arteries from hypertensive rats and were not mimicked by the KV7.1-specific activator R-L3. In isolated, perfused heart preparations, coronary flow rate increased in response to the KV7.2 to 7.5 activator (S)-1 and was diminished in the presence of a KV7 inhibitor. The expression levels of KCNQ1-5 and their known accessory KCNE1-5 subunits in coronary arteries were similar in normotensive and hypertensive rats as measured by quantitative polymerase chain reaction. However, KV7.4 protein expression was reduced in hypertensive rats. Application of adenosine or A2A receptor agonist CGS-21680 produced concentration-dependent relaxations of coronary arteries from normotensive rats, which were attenuated by application of KV7 inhibitors. KV7 blockers also attenuated the ischemia-induced increase in coronary perfusion in Langendorff studies. Overall, these data establish KV7 channels as crucial regulators of coronary flow at resting and after hypoxic insult.

AB - The goal of the present study was to determine the role of KCNQ-encoded KV channels (KV7 channels) in the passive and active regulation of coronary flow in normotensive and hypertensive rats. In left anterior descending coronary arteries from normotensive rats, structurally different KV7.2 to 7.5 activators produced relaxations, which were considerably less in arteries from hypertensive rats and were not mimicked by the KV7.1-specific activator R-L3. In isolated, perfused heart preparations, coronary flow rate increased in response to the KV7.2 to 7.5 activator (S)-1 and was diminished in the presence of a KV7 inhibitor. The expression levels of KCNQ1-5 and their known accessory KCNE1-5 subunits in coronary arteries were similar in normotensive and hypertensive rats as measured by quantitative polymerase chain reaction. However, KV7.4 protein expression was reduced in hypertensive rats. Application of adenosine or A2A receptor agonist CGS-21680 produced concentration-dependent relaxations of coronary arteries from normotensive rats, which were attenuated by application of KV7 inhibitors. KV7 blockers also attenuated the ischemia-induced increase in coronary perfusion in Langendorff studies. Overall, these data establish KV7 channels as crucial regulators of coronary flow at resting and after hypoxic insult.

U2 - 10.1161/hypertensionaha.113.01244

DO - 10.1161/hypertensionaha.113.01244

M3 - Journal article

C2 - 24082059

SN - 0194-911X

VL - 62

SP - 1090

EP - 1097

JO - Hypertension

JF - Hypertension

IS - 6

ER -