Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: Involvement of nitric oxide

Yu Long Li, Shu Yu Sun, Jeffery L. Overholt, Nanduri R. Prabhakar, George J. Rozanski, Irving H. Zucker, Harold D. Schultz

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

It has been shown that peripheral chemoreceptor sensitivity is enhanced in both clinical and experimental heart failure (HF) and that impairment of nitric oxide (NO) production contributes to this enhancement. In order to understand the cellular mechanisms associated with the alterations of chemoreceptor function and the actions of NO in the carotid body (CB), we compared the outward K+ currents (IK) of glomus cells in sham rabbits with that in HF rabbits and monitored the effects of NO on these currents. Ik was measured in glomus cells using conventional and perforated whole-cell configurations. IK was attenuated in glomus cells of HF rabbits, and their resting membrane potentials (-34.7 ± 1.0 mV) were depolarized as compared with those in sham rabbits (-47.2 ± 1.9 mV). The selective Ca2+-dependent K+ channel (KCa) blocker iberiotoxin (IbTx, 100 nm) reduced IK in glomus cells from sham rabbits, but had no effect on IK from HF rabbits. In perforated whole-cell mode, the NO donor SNAP (100 μm) increased IK in glomus cells from HF rabbits to a greater extent than that in sham rabbits (P < 0.01), and IbTx inhibited the effects of SNAP. However, in conventional whole-cell mode, SNAP had no effect. Nω-nitro-L-arginine (L-NNA, NO synthase inhibitor) decreased Ik in sham rabbits but not in HF rabbits. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) inhibited the effect of SNAP on Ik. These results demonstrate that IK is reduced in CB glomus cells from HF rabbits. This effect is due mainly to the suppression of KCa channel activity caused by decreased availability of NO. In addition, intracellular cGMP is necessary for the KCa channel modulation by NO.

Original languageEnglish (US)
Pages (from-to)219-229
Number of pages11
JournalJournal of Physiology
Volume555
Issue number1
DOIs
StatePublished - Feb 15 2004

ASJC Scopus subject areas

  • Physiology

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