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Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: involvement of nitric oxide
Author(s) -
Li YuLong,
Sun ShuYu,
Overholt Jeffery L.,
Prabhakar Nanduri R.,
Rozanski George J.,
Zucker Irving H.,
Schultz Harold D.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.057422
Subject(s) - glomus cell , carotid body , snap , nitric oxide , nitric oxide synthase , chemistry , iberiotoxin , medicine , endocrinology , lagomorpha , channel blocker , chemoreceptor , potassium channel , electrophysiology , receptor , calcium , computer graphics (images) , computer science
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 ( I K ) of glomus cells in sham rabbits with that in HF rabbits and monitored the effects of NO on these currents. I k was measured in glomus cells using conventional and perforated whole‐cell configurations. I K 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 Ca 2+ ‐dependent K + channel (K Ca ) blocker iberiotoxin (IbTx, 100 n m ) reduced I K in glomus cells from sham rabbits, but had no effect on I K from HF rabbits. In perforated whole‐cell mode, the NO donor SNAP (100 μ m ) increased I K 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. N ω ‐nitro‐ L ‐arginine (L‐NNA, NO synthase inhibitor) decreased I k 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 I k . These results demonstrate that I K is reduced in CB glomus cells from HF rabbits. This effect is due mainly to the suppression of K Ca channel activity caused by decreased availability of NO. In addition, intracellular cGMP is necessary for the K Ca channel modulation by NO.