TY - JOUR
T1 - Reduced functional expression of K+ channels in vascular smooth muscle cells from rats made hypertensive with Nω-nitro-L- arginine
AU - Bratz, Ian N.
AU - Swafford, Albert N.
AU - Kanagy, Nancy L.
AU - Dick, Gregory M.
PY - 2005/9
Y1 - 2005/9
N2 - 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 Nω-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+ (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 Ca 2+-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 BK Ca 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.
AB - 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 Nω-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+ (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 Ca 2+-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 BK Ca 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.
KW - Ca-activated K channel
KW - Delayed rectifier K channel
KW - Hypertension
KW - Membrane potential
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=23944512766&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.01053.2004
DO - 10.1152/ajpheart.01053.2004
M3 - Article
C2 - 15879481
AN - SCOPUS:23944512766
SN - 0363-6135
VL - 289
SP - H1284-H1290
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3 58-3
ER -