| Abstrakt: |
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-HI283, 2005), we demonstrated that superior mesenteric arteries from rats made hypertensive with Nɷ-nitro-L-arginine (LNNA) 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+ (KV) channels, was reduced ∼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 ∼40% by hypertension (181 ± 24 vs. 101 ± 28 pA/pF). Current blocked by 3 mM 4-aminopyridine, an inhibitor of many KV channel types, was reduced ∼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 ∼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. [ABSTRACT FROM AUTHOR] |
