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

Smooth muscle membrane potential (E-m) depends on K+ channels, and arteries from rats made hypertensive with N-omega-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+ (BKCa) channels, depolarized control and LHR E-m 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+ (K-V) channel blocker 4-amino-pyridine (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 K(V)1.5 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 K-V channel function in control and LHR smooth muscle cells.