Contribution of Voltage‐Dependent Potassium & Calcium Channels to Coronary Pressure‐Flow Autoregulation

Abstract

The goal of this investigation was to test the hypothesis that voltage‐sensitive potassium (KV) and calcium (CaV1.2) channels contribute to coronary pressure‐flow autoregulation in vivo. This hypothesis was tested in open‐chest, anaesthetized Ossabaw swine during step changes in coronary perfusion pressure (CPP) from 140‐40 mmHg before/during inhibition of KV channels with 4AP (0.3 mM, ic) or CaV1.2 channels with diltiazem (10 μg/min, ic). 4AP significantly decreased vasodilatory responses to H2O2 (0.3 – 10 μg/min) and blood flow at CPPs = 140‐60 mmHg. This decrease in coronary flow was associated with diminished ventricular contractile function (dP/dT) and myocardial oxygen consumption. However, the overall sensitivity to changes in CPP from 120 to 60 mmHg (i.e. autoregulatory gain; Gc) was unaltered by 4‐AP administration (Gc = 0.35 ± 0.11 control vs. 0.39 ± 0.07 4‐AP). In contrast, diltiazem markedly increased coronary blood flow at CPPs > 80 mmHg and decreased coronary autoregulatory gain (Gc = −0.21 ± 0.08) relative to control (P < 0.01), with no effect on contractile function or oxygen consumption. Taken together, our findings demonstrate that: 1) KV channels tonically contribute to the control of vascular resistance over a wide range of CPPs; 2) CaV1.2 channels play a critical role in coronary pressure‐flow autoregulation.