Diabetic dyslipidemia and exercise affect coronary tone and differential regulation of conduit and microvessel K+ current

Spontaneous transient outward K+ currents (STOCs) elicited by Ca2+ sparks and steady-state K+ currents modulate vascular reactivity, but effects of artery size, diabetic dyslipidemia, and exercise on these differentially regulated K+ currents are unclear. We studied the conduit arteries and microvessels of male Yucatan swine assigned to one of three groups for 20 wk: control (C, n = 7), diabetic dyslipidemic (DD, n = 6), or treadmill-trained DD animals (DDX, n = 7). Circumflex artery blood flow velocity obtained with intracoronary Doppler and lumen diameters obtained by intravascular ultrasound enabled calculation of absolute coronary blood flow (CBF). Ca2+ sparks were determined in pressurized microvessels, and perforated patch clamp assessed K+ current in smooth muscle cells isolated from conduits and microvessels. Baseline CBF in DD was decreased versus C. In pressurized microvessels, Ca2+ spark activity was significantly lower in DD versus C and DDX (P <0.05 vs. DDX). STOCs were pronounced in microvessel (∼35 STOCs/min) in sharp contrast to conduit cells (∼2 STOCs/min). STOCs were decreased by 86% in DD versus C and DDX in microvessels; in contrast, there was no difference in STOCs across groups in conduit cells. Steady-state K+ current in microvessels was decreased in DD and DDX versus C; in contrast, steady-state K+ current in conduit cells was decreased in DDX versus DD and C. We conclude that steady-state K+ current and STOCs are differentially regulated in conduit versus microvessels in health and diabetic dyslipidemia. Exercise prevented diabetic dyslipidemia-induced decreases in baseline CBF, possibly via STOC-regulated basal microvascular tone.