Aging decreases the contribution of MaxiK channel in regulating vascular tone in mesenteric artery by unparallel downregulation of α- and β1-subunit expression

Abstract

Vascular disease increases in incidence with age and is the commonest cause of morbidity and mortality among elderly people. Large-conductance Ca(2+)-activated K(+)(MaxiK) channel, with pore-forming α-subunit and modulatory β1-subunit, is a key regulator of vascular tone. This study explored functional and molecular evidence of MaxiK alteration with aging in the mesenteric artery(MA). Young, Middle-aged, and Old male Wistar rats were used. Selective MaxiK channel blocker (Iberiotoxin) induced a significant increase of vascular tension in MA in all three age groups. However, these effects were greatly decreased in Old animals. The amplitude and frequency of spontaneous transient outward currents were significantly decreased with aging. Single channel recording revealed that aging induced a decrease of the open probability and the mean open time, but an increase of the mean closed time of MaxiK channel. The Ca(2+)/voltage sensitivity of MaxiK was also decreased. Western blotting showed that the protein expression of MaxiK β1- and α-subunit was significantly reduced with aging, and the suppression of β1 subunits was larger than that of α subunits. These data suggest that aging decreases capability of MaxiK channel in regulating vascular tone in the MA, which may be partially mediated by unparallel downregulation of α- and β1-subunit expression.

Keywords: Aging; BP; BW; CVDs; DBP; G; HP; HR; HW; IbTX; MA; MaxiK (or BK(Ca)); MaxiK channel; Mesenteric artery; PP; PSS I; Po; SBP; SMCs; STOCs; TEA; Tc; To; VSMCs; Vascular smooth muscle cell; [Ca(2+)](i); blood pressure; body weight; cardiovascular diseases; conductance; diastolic blood pressure; heart rate; heart weight; holding potential; iberiotoxin; intracellular Ca(2+) concentration; large-conductance Ca(2+)-activated K(+); mean close time; mean open time; mesenteric artery; open probability; physiological salt solution I; pulse pressure; smooth muscle cells; spontaneous transient outward currents; systolic blood pressure; tetraethylammonium; vascular smooth muscle cells.