Reduced functional expression of K+ channels in vascular smooth muscle cells from rats made hypertensive with Nω-nitro-L-arginine

Smooth muscle membrane potential is determined, in part, by K+ channels. In the companion paper to this article (Bratz IN, Dick GM, Partridge LD, and Kanagy NL. Am J Physiol Heart Circ Physiol 289: H1277-H1283, 2005), we demonstrated that superior mesenteric arteries from rats made hypertensive with N-omega-nitro-L-arginine (L-NNA) are depolarized and express less K+ channel protein compared with those from normotensive rats. In the present study, we used patch-clamp techniques to test the hypothesis that L-NNA-induced hypertension reduces the functional expression of K+ channels in smooth muscle. In whole cell experiments using a Ca2+-free pipette solution, current at 0 mV, largely due to voltage-dependent K+ (K-V) channels, was reduced similar to 60% by hypertension (2.7 +/- 0.4 vs. 1.1 +/- 0.2 pA/pF). Current at +100 mV with 300 nM free Ca2+, largely due to large-conductance Ca2+-activated K+ (BKCa) channels, was reduced similar to 40% by hypertension (181 +/- 24 vs. 101 +/- 28 pA/pF). Current blocked by 3 mM 4-aminopyridine, an inhibitor of many K-V channel types, was reduced similar to 50% by hypertension (1.0 +/- 0.4 vs. 0.5 +/- 0.2 pA/pF). Current blocked by 1 mM tetraethylammonium, an inhibitor of BKCa channels, was reduced similar to 40% by hypertension (86 +/- 14 vs. 53 +/- 19 pA/pF). Differences in BKCa current magnitude are not attributable to changes in single-channel conductance or Ca2+/voltage sensitivity. The data support the hypothesis that L-NNA-induced hypertension reduces K+ current in vascular smooth muscle. Reduced molecular and functional expression of K+ channels may partly explain the depolarization and augmented contractile sensitivity of smooth muscle from L-NNA-treated rats.