Roles of K+ and Cl- Channels in cAMP-induced pulmonary vasodilation

Yi Ju Zhao, Jian Wang, Lewis J. Rubin, Xiao Jian Yuan

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Increase in intracellular adenosine 3', 5'-cyclic monophosphate (cAMP) is a common pathway for many clinically used drugs to cause pulmonary artery (PA) relaxation. Activity of sarcolemmal K+ and C-channels is an important determinant of membrane potential E(m)), which, in turn, plays a critical role in regulating pulmonary vascular tone. Whether K+ and C- channels were involved in cAMP-induced PA relaxation was tested using isolated rat PA rings. Raising extracellular K+ concentration from 20 to 142. 7 mM increased the K+-evoked contraction, but significantly decreased the relaxation induced by the adenylate cyclase activator, forskolin (FSK, 2.5 μM), suggesting that FSK-induced PA relaxation depended on transmembrane K+ gradient. Indeed, the FSK-induced relaxation was inhibited by 4- aminopyridine (4-AP, 10 raM), a voltage-gated K+ (K(v)) channel blocker. Neither the Ca2+-activated K+ channel blocker, charybdotoxin, nor the ATP- sensitive K+ channel blocker, glibenclamide, had this effect. Furthermore, reducing extracellular Cl- concentration from 142.7 to 50 mM significantly decreased the FSK-induced relaxation in PA rings precontracted with 142.7 mM K+ (E(k) ≃ 0 mV), but negligibly affected the evoked contraction. This indicates that transmembrane Cl- gradient also regulates FSK-induced PA relaxation. Indeed, the Cl- channel blocker, 5-nitro-2-(3- phenylpropylamino)benzoic acid (NPPB, 10 μM), significantly inhibited the FSK-induced relaxation in PA rings preconstricted by 142.7 mM K+. In summary, the data suggest that the cAMP-induced PA relaxation is attributable, at least partly, to both activation of the 4-AP-sensitive K(v) channels and stimulation of the NPPB-sensitive Cl- channels.

Original languageEnglish (US)
Pages (from-to)71-83
Number of pages13
JournalExperimental Lung Research
Volume24
Issue number1
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Keywords

  • 4-aminopyridine
  • CAMP
  • Channel
  • Cl
  • Forskolin
  • K channel

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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