Reduced molecular expression of K(+) channel proteins in vascular smooth muscle from rats made hypertensive with N{omega}-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 (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.
Bratz
Ian N
IN
Department of Physiology, LSU Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA.
Dick
Gregory M
GM
Partridge
L Donald
LD
Kanagy
Nancy L
NL
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
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019335:Nitroarginine; D011188:Potassium