Gender regulation of expression of the KCNE3 regulatory β‐subunit of the KCNQ1 channel in rat colonic crypts

Abstract

The KCNQ1 potassium channel associates with various KCNE β-subunits that drastically affect channel gating and pharmacology. Co-assembly of KCNQ1 with KCNE3 produces a current with nearly instantaneous activation, some time-dependent activation at very positive potentials, a linear current-voltage relationship and a 10-fold higher sensitivity to chromanol 293B. KCNQ1/KCNE3 channels are expressed in colonic crypts and mediate basolateral K+ recycling required for Cl− secretion. This study was designed to determine whether gender regulates the expression and function of KCNQ1/KCNE3 in rat distal colon. Colonic crypts were isolated from Sprague-Dawley rats and used for whole-cell patch-clamp and to extract total RNA and protein. Sheets of epithelium were used for short circuit current recordings. The abundance of KCNE3 mRNA and protein was significantly higher in male than female crypts while no difference was observed in KCNQ1 expression. In male crypts, patch-clamp recordings showed a linear current-voltage relationship, while female crypts showed voltage-dependent outward rectification. Currents in male crypts and epithelial sheets were 10-fold more sensitive to chromanol 293B than in female. Together, these results suggest that gender regulates the expression of the KCNE3 and thus the properties of the K+ conductance required for Cl− secretion. Supported by The Wellcome Trust and HEA PRTLI Programme Grant.