Reduced functional expression of K(+) channels in vascular smooth muscle cells from rats made hypertensive with N{omega}-nitro-L-arginine.
Smooth muscle membrane potential is determined, in part, by K(+) channels. In the companion paper to this article, 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 Ca(2+)-free pipette solution, current at 0 mV, largely due to voltage-dependent K(+) (K(V)) channels, was reduced approximately 60% by hypertension (2.7 +/- 0.4 vs. 1.1 +/- 0.2 pA/pF). Current at +100 mV with 300 nM free Ca(2+), largely due to large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels, was reduced approximately 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 approximately 50% by hypertension (1.0 +/- 0.4 vs. 0.5 +/- 0.2 pA/pF). Current blocked by 1 mM tetraethylammonium, an inhibitor of BK(Ca) channels, was reduced approximately 40% by hypertension (86 +/- 14 vs. 53 +/- 19 pA/pF). Differences in BK(Ca) current magnitude are not attributable to changes in single-channel conductance or Ca(2+)/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.
Bratz
Ian N
IN
Department of Physiology, LSU Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA.
Swafford
Albert N
AN
Kanagy
Nancy L
NL
Dick
Gregory M
GM
D000818:Animals; D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D019335:Nitroarginine; D009569:Nitric Oxide