Contribution of Na+-K+ pump and KIR currents to extracellular pH-dependent changes of contractility in rat superior mesenteric artery.
We compared the branches and trunk of rat superior mesenteric artery (SMA) with respect to extracellular pH (pHo)-dependent changes in vascular contractility. Decreases in pHo from 7.8 to 6.4 significantly reduced apparent affinity (pD2) to norepinephrine (NE) and maximal contraction by NE, which were more prominent in larger-diameter arteries. On the other hand, decreases in pHo significantly reduced Ba2+-sensitive K+-induced relaxation (which was evoked by elevation of extracellular K+ concentration from 6 to 12 mM) in the first branch and inhibited inwardly rectifying K+ (K(IR)) currents in cultured smooth muscle cells (SMCs) of SMA. RT-PCR revealed transcripts for Kir2.1 in the SMCs. Real-time PCR analysis revealed 6.1-, 3.3-, and 2.2-fold increases in the Kir2.1 mRNA-to-beta-actin mRNA ratios of SMCs of the third, second, and first branches, respectively, vs. the corresponding relative levels of trunk SMCs. The magnitudes of K+-induced relaxation were significantly greater in smaller-diameter arteries, and there was a strong correlation between the transcript levels of Kir2.1 and K+-induced relaxation. A decrease in pHo reduced ouabain-sensitive K+-induced relaxation and ouabain-induced contraction. A decrease in pHo from 7.4 to 6.4 depolarized membrane potential of the cultured SMCs. From these results, we conclude that an increase in pHo activates K(IR) currents and the Na+ -K+ pump, which then reduces vascular contractility. Inasmuch as K(IR) channel densities are significantly greater in smaller-diameter arteries, the reduction in vascular contractility on increasing pHo is more pronounced in smaller-diameter arteries.
Kim
Moon Young
MY
Department of Physiology and Medical Research Institute, College of Medicine, Ewha Women's Univ., 911-1 Mok-6-dong, Yang Chun-gu, Seoul, Republic of Korea, 158-710.
Liang
Guo Hua
GH
Kim
Ji Aee
JA
Park
Seong Hoon
SH
Hah
Jong Sik
JS
Suh
Suk Hyo
SH
D000818:Animals; D004553:Electric Conductivity; D045604:Extracellular Fluid / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008564:Membrane Potentials; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation
C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D011522:Protons; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium