Reduced molecular expression of K+ channel proteins in vascular smooth muscle from rats made hypertensive with Nω-nitro-L- arginine

Ian N. Bratz, Gregory M. Dick, L. Donald Partridge, Nancy L. Kanagy

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Smooth muscle membrane potential (Em) depends on K+ channels, and arteries from rats made hypertensive with Nω- nitro-L-arginine (LHR) are depolarized compared with control. We hypothesized that decreased K+ channel function, due to decreased K+ channel protein expression, underlies Em depolarization. Furthermore, K+ channel blockers should move control Em (-46 ± 1 mV) toward that in LHR (-37 ± 2 mV) and normalize contraction. The Em vs. K+ relationship was less steep in LHR (23 ± 2 vs. 28 ± 1 mV/log K+ concentration), and contractile sensitivity to K+ was increased (EC50 = 37 ± 1 vs. 23 ± 1 mM). Iberiotoxin (10 nM), an inhibitor of large-conductance Ca2+-activated K+ (BKCa) channels, depolarized control and LHR Em 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+ (Kv) channel blocker 4-amino-pyridine (3 mM) depolarized control Em to the level of LHR (-28 ± 1 vs. -28 ± 1 mV); however, effects on K+ sensitivity were greater in LHR (EC50 = 17 ± 4 vs. 4 ± 4 mM). Western blots revealed reduced BKCa and Kv1.5 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 BKCa and Kv channel function in control and LHR smooth muscle cells [see companion paper (Bratz IN, Swafford AN Jr, Kanagy NL, and Dick GM. Am J Physiol Heart Circ Physiol 289: H1284-H1290, 2005)].

Original languageEnglish
Pages (from-to)H1277-H1283
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number3 58-3
DOIs
StatePublished - 1 Sep 2005

Keywords

  • 4-aminopyridine
  • Iberiotoxin
  • Membrane potential
  • Nitric oxide

Fingerprint Dive into the research topics of 'Reduced molecular expression of K<sup>+</sup> channel proteins in vascular smooth muscle from rats made hypertensive with N<sup>ω</sup>-nitro-L- arginine'. Together they form a unique fingerprint.

  • Cite this