CA2+-DEPENDENT K+ CURRENT IN ARTERIAL SMOOTH-MUSCLE CELLS FROM ALDOSTERONE-SALT HYPERTENSIVE RATS

Aorta from aldosterone-salt hypertensive rats (AHR) demonstrates an increased basal K-42 efflux. We investigated the cellular mechanisms of this alteration by measuring K-42 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 K-42 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 Ca2+-activated, voltage-dependent K+ (K-Ca) 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 K-Ca 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 K-42 efflux responses to caffeine were greater in AHR. After continued exposure to caffeine, the basal K-42 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 K-42 efflux and K+ current reflect an increased activity of K-Ca 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.