Differences in K + current components in mesenteric artery myocytes from WKY and SHR

Abstract

Previous studies have documented increased K + permeability of arterial smooth muscle in hypertension and suggested a role in altered arterial contractile function. To characterize the mechanisms responsible for these alterations, we determined the contribution of K + current (I K) components to whole cell I K in freshly dispersed myocytes and tetraethylammonium (TEA)-induced contractile responses in mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tetraethylammonium produced a larger tonic contractile response in SHR with a lower threshold compared to WKY (ie, 0.1 v 1 mmol/L), which was due in part to the larger Ca 2+ current in SHR. Whole cell I K recorded by perforated patch methods was similar at a holding potential (HP) of −60 mV (I K60), but were larger in SHR when recorded from a HP of −20 mV (I K20). The selective blocker iberiotoxin (IbTX) was used to separate the contribution of voltage- (K V) and calcium-dependent (K Ca) components of I K60. The I K60 and I K20 component inhibited by 100 nmol/L IbTX (ie, K Ca) was larger in SHR than in WKY myocytes, whereas the IbTX-insensitive I K60 component (ie, K V) was larger in WKY. In the presence of IbTX, 1 and 10 mmol/L TEA inhibited a larger fraction of I K60 in SHR myocytes compared with WKY. The activation properties of the TEA-sensitive and TEA-insensitive K V components determined by fitting a Boltzmann activation function to the current-voltage data, exhibited both group and treatment differences in the half maximal activation voltage (V 0.5). The V 0.5 of the TEA-sensitive K V component was more positive than that of the TEA-insensitive component in both groups, and values for the V 0.5 of both TEA-sensitive and TEA-insensitive components were more negative in SHR than WKY. These results show that SHR myocytes have larger K Ca and smaller K V current components compared with WKY. Furthermore, SHR myocytes have a larger TEA-sensitive K V component. These differences may contribute to the differences in TEA contractions, resting membrane potential, Ca 2+ influx, and K Ca current reported in hypertensive arteries.