Ca(2+)-dependent K+ current in arterial smooth muscle cells from aldosterone-salt hypertensive rats.

Abstract

Aorta from aldosterone-salt hypertensive rats (AHR) demonstrates an increased basal 42K efflux. We investigated the cellular mechanisms of this alteration by measuring 42K efflux from aortic segments as well as myoplasmic Ca2+ concentration ([Ca2+]m) and K+ current in aortic smooth muscle cells from AHR and normotensive control-salt rats (CSR). Both diltiazem and nisoldipine attenuated but did not normalize the increase in basal 42K efflux in AHR. The resting [Ca2+]m was elevated in cells from AHR (148 +/- 15 vs. 91 +/- 12 nM for CSR, P < 0.05). The rate of Mn2+ quenching under basal conditions was also increased in cells from AHR, and the increase was abolished by Cd2+. However, the resting membrane potential did not differ between CSR and AHR (-49 +/- 5 vs. -50 +/- 4 mV). The steady-state, whole cell K+ current was also increased in cells from AHR. This increase was abolished by charybdotoxin, tetraethylammonium, La3+, and by clamping [Ca2+]m at zero or 100 nM with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. The single-channel conductance of the large conductance Ca(2+)-activated, voltage-dependent K+ (KCa) channels was not altered in AHR. Further, 33% of cells from AHR vs. 1% from CSR showed spontaneous transient outward K+ currents, which reflect activation of KCa channels by Ca2+ released from caffeine-sensitive stores. While the acute caffeine-induced [Ca2+]m response was similar between CSR and AHR, the outward current and 42K efflux responses to caffeine were greater in AHR. After continued exposure to caffeine, the basal 42K efflux was attenuated more in AHR than in CSR. Charybdotoxin resulted in a greater depolarization in AHR cells than in CSR cells (9.8 +/- 2.2 vs. 3.5 +/- 1.6 mV, P < 0.05). These results indicate that the increases in both 42K efflux and K+ current reflect an increased activity of KCa channels that is associated with an increased Ca2+ influx and resting [Ca2+]m and altered Ca2+ handling by the sarcoplasmic reticulum in aortic smooth muscle cells from AHR.