Reduced molecular expression of K⁺ channel proteins in vascular smooth muscle from rats made hypertensive with N^ω-nitro-L- arginine

Smooth muscle membrane potential (E_m) depends on K⁺ channels, and arteries from rats made hypertensive with N^ω- nitro-L-arginine (LHR) are depolarized compared with control. We hypothesized that decreased K⁺ channel function, due to decreased K⁺ channel protein expression, underlies E_m depolarization. Furthermore, K⁺ channel blockers should move control E_m (-46 ± 1 mV) toward that in LHR (-37 ± 2 mV) and normalize contraction. The E_m vs. K⁺ relationship was less steep in LHR (23 ± 2 vs. 28 ± 1 mV/log K⁺ concentration), and contractile sensitivity to K⁺ was increased (EC₅₀ = 37 ± 1 vs. 23 ± 1 mM). Iberiotoxin (10 nM), an inhibitor of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels, depolarized control and LHR Em to -35 ± 1 and -30 ± 2 mV, respectively; however, effects on K⁺ sensitivity were more profound in LHR (EC ₅₀ = 25 ± 2 vs. 15 ± 3 mM). The voltage-dependent K⁺ (K_v) channel blocker 4-amino-pyridine (3 mM) depolarized control E_m to the level of LHR (-28 ± 1 vs. -28 ± 1 mV); however, effects on K⁺ sensitivity were greater in LHR (EC₅₀ = 17 ± 4 vs. 4 ± 4 mM). Western blots revealed reduced BK_Ca and K_v1.5 channel expression in LHR arteries. The findings suggest that diminished expression of K⁺ channels contributes to depolarization and enhanced contractile sensitivity. These conclusions are supported by direct electrophysiological assessment of BK_Ca and K_v channel function in control and LHR smooth muscle cells [see companion paper (Bratz IN, Swafford AN Jr, Kanagy NL, and Dick GM. Am J Physiol Heart Circ Physiol 289: H1284-H1290, 2005)].