The G protein-coupled estrogen receptor agonist, G-1, attenuates BK channel activation in cerebral arterial smooth muscle cells.

Abstract

The G protein–coupled estrogen receptor (GPER) is a significant modulator of arterial contractility and blood flow. The GPER‐specific activator, G‐1, has been widely used to characterize GPER function in a variety of tissue types. Large conductance, calcium (Ca2+)‐activated K+ (BK) channels are sensitive to 17β‐estradiol (17β‐E2) and estrogenic compounds (e.g., tamoxifen, ICI 182 780) that target estrogen receptors. The purpose of this study was to investigate the effects of G‐1 on BK channel activation and function in cerebral arterial myocytes. Inside‐out and perforated patch clamp were utilized to assess the effects of G‐1 (50 nmol·L−1‐5 μmol·L−1) on BK channel activation and currents in cerebral arterial myocytes. Pressurized artery myography was used to investigate the effects of G‐1 on vasodilatory response and BK channel function of cerebral resistance size arteries. G‐1 reduced BK channel activation in cerebral arterial myocytes through elevations in BK channel mean close times. Depressed BK channel activation following G‐1 application resulted in attenuated physiological BK currents (transient BK currents). G‐1 elicited vasodilation, but reduced BK channel function, in pressurized, endothelium‐denuded cerebral arteries. These data suggest that G‐1 directly suppresses BK channel activation and currents in cerebral arterial myocytes, BK channels being critically important in the regulation of myocyte membrane potential and arterial contractility. Thus, GPER‐mediated vasodilation using G‐1 to activate the receptor may underestimate the physiological function and relevance of GPER in the cardiovascular system.