Involvement of sex hormonal regulation of K+ channels in electrophysiological and contractile functions of muscle tissues

Sex hormones, such as testosterone, progesterone, and 17 beta-estradiol, control various physiological functions. This review focuses on the sex hormonal regulation of K+ channels and the effects of such regulation on electrophysiological and contractile functions of muscles. In the cardiac tissue, testosterone and progesterone shorten action potential, and estrogen lengthens QT interval, a marker of increased risk of ventricular tachyarrhythmias. We have shown that testosterone and progesterone in physiological concentration activate KCNQ1 channels via membrane-delimited sex hormone receptor/eNOS pathways to shorten the action potential duration. Mitochondrial K+ channels are also involved in the protection of cardiac muscle. Testosterone and 17 beta-estradiol directly activate mitochondrial inner membrane K channels (Ca2+ activated K+ channel (KCa channel) and ATP-sensitive K+ channel (KATP channel)) that are involved in ischemic preconditioning and cardiac protection. During pregnancy, uterine blood flow increases to support fetal growth and development. It has been reported that 17 beta-estradiol directly activates large-conductance Ca2+ -activated K+ channel (BKCa channel) attenuating arterial contraction. Furthermore, 17 beta-estradiol increases expression of BKCa channel b1 subunit which enhances BKCa channel activity by DNA demethylation. These findings are useful for understanding the mechanisms of sex or generation-dependent differences in the physiological and pathological functions of muscles, and the mechanisms of drug actions. (c) 2019 The Authors. Production and hosting by Elsevier B. V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/ licenses/by-nc-nd/4.0/).