Influence of sex, high-fat diet, and exercise training on potassium currents of swine coronary smooth muscle

Abstract

Potassium channels in vascular smooth muscle (VSM) control vasodilation and are potential regulatory targets. This study evaluated effects of sex differences, exercise training (EX), and high-fat diet (HF) on K+ currents ( IK) of coronary VSM cells. Yucatan male and female swine were assigned to either sedentary confinement (SED), 16 wk of EX, 20 wk of HF, or 20 wk of HF with 16 wk of EX (HF-EX). VSM cells of normal-diet SED animals exhibited three components of IK: 4-aminopyridine-sensitive IK(KV), TEA-sensitive IK(BK), and 4-aminopyridine + TEA-insensitive IK. Females exhibited significantly higher basal IK than males in the same group. EX increased basal IK in males and females. HF reduced IK in males and females and nullified effects of EX. Endothelin-1 increased IK significantly in males but not in females. In the presence of endothelin-1, 1) IK(KV) was similar in SED males and females and EX increased IK(KV) to a greater extent in males than in females and 2) IK(BK) was greater in SED females than in males and EX increased IK(BK) to a greater extent in males, resulting in IK(BK) similar to EX females. Importantly, HF nullified effects of EX on IK(KV) and IK(BK). These data indicate that basal IK of SED female swine is inherently greater than that shown in SED males and that males require EX to achieve comparable levels of IK. Importantly, HF reduced IK in males and females and nullified effects of EX, suggesting HF abrogates beneficial effects of EX on coronary smooth muscle.