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

Aorta from aldosterone-salt hypertensive rats (AHR) demonstrates an in creased 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 i ncrease in basal K-42 efflux in AHR. The resting [Ca2+](m) was elevate d in cells from AHR (148 +/- 15 vs. 91 +/- 12 nM for CSR, P < 0.05). T he rate of Mn2+ quenching under basal conditions was also increased in cells from AHR, and the increase was abolished by Cd2+ However, the r esting 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 charybdoto xin, tetraethylammonium, La3+, and by clamping [Ca2+](m) at zero or 10 0 nM with ethylene glycol-bis(beta-aminoethyl ether)N,N,N' ,N'-tetraac etic acid. The single-channel conductance of the large conductance Ca2 +-activated, voltage-dependent K+ (K-Ca) channels was not altered in A HR. Further, 33% of cells from AHR vs. 1% from CSR showed spontaneous transient outward K+ currents, which reflect activation of K-Ca channe ls by Ca2+ released from caffeine-sensitive stores. While the acute ca ffeine-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 greate r 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 bot h K-42 efflux and K+ current reflect an increased activity of K-Ca cha nnels that is associated with an increased Ca2+ influx and resting [Ca 2+](m) and altered Ca2+ handling by the sarcoplasmic reticulum in aort ic smooth muscle cells from AHR.