Smooth muscle membrane potential ( Em) depends on K+ channels, and arteries from rats made hypertensive with Nω-nitro-l-arginine (LHR) are depolarized compared with control. We hypothesized that decreased K+ channel function, due to decreased K+ channel protein expression, underlies Em depolarization. Furthermore, K+ channel blockers should move control Em (−46 ± 1 mV) toward that in LHR (−37 ± 2 mV) and normalize contraction. The Em 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+ (BKCa) channels, depolarized control and LHR Em to −35 ± 1 and −30 ± 2 mV, respectively; however, effects on K+ sensitivity were more profound in LHR (EC50 = 25 ± 2 vs. 15 ± 3 mM). The voltage-dependent K+ (KV) channel blocker 4-aminopyridine (3 mM) depolarized control Em 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 BKCa and KV1.5 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 BKCa and KV 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)].
Structural motifs underlying voltage-dependent K+ channel function
