title: Reduced molecular expression of K(+) channel proteins in vascular smooth muscle from rats made hypertensive with N{omega}-nitro-L-arginine.
abstract: 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 (EC(50) = 37 +/- 1 vs. 23 +/- 1 mM). Iberiotoxin (10 nM), an inhibitor of large-conductance Ca(2+)-activated K(+) (BK(Ca)) 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 (EC(50) = 25 +/- 2 vs. 15 +/- 3 mM). The voltage-dependent K(+) (K(V)) channel blocker 4-aminopyridine (3 mM) depolarized control E(m) to the level of LHR (-28 +/- 1 vs. -28 +/- 1 mV); however, effects on K(+) sensitivity were greater in LHR (EC(50) = 17 +/- 4 vs. 4 +/- 4 mM). Western blots revealed reduced BK(Ca) 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 BK(Ca) and K(V) channel function in control and LHR smooth muscle cells.
authors.affiliation: Department of Physiology, LSU Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA.
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bratz
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Dick
authors.forename: L Donald
authors.initials: LD
authors.lastname: Partridge
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Kanagy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004791:Enzyme Inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008638:Mesenteric Arteries / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019335:Nitroarginine; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019335:Nitroarginine; D011188:Potassium