Faculty Collaboration Database

Nitration and functional loss of voltage-gated K+ channels in rat coronary microvessels exposed to high glucose. Diabetes 2004 Sep;53(9):2436-42

Date

08/28/2004

Pubmed ID

15331556

DOI

10.2337/diabetes.53.9.2436

Scopus ID

2-s2.0-4344628116 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

Coronary microvessels generate reactive oxygen species in response to high glucose (HG), resulting in vasodilator defects involving an impaired function of vascular K(+) channels. Inhibition of voltage-gated K(+) (K(v)) channels by peroxynitrite (ONOO(-)), formed by the interaction of superoxide and nitric oxide, may contribute to impaired dilation. The present study investigated whether HG induces ONOO(-) formation to mediate nitration and impairment of K(v) channels in rat small coronary arteries (RSCAs). Exposure to ONOO(-) reduced the dilator influence of K(v) channels in RSCAs. Patch-clamp studies revealed that ONOO(-) diminished whole-cell and unitary K(v) currents attributable to the K(v)1 gene family in smooth muscle cells. Subsequently, immunohistochemically detected enhancement of nitrotyrosine residues in RSCAs that were cultured in HG (23 mmol/l) compared with normal glucose (5.5 mmol/l) for 24 h correlated with the nitration of K(v)1.2 channel alpha-subunits. HG-induced nitrotyrosine formation was partially reversed by scavenging ONOO(-). Finally, RSCAs that were exposed to HG for 24 h showed a loss of K(v) channel dilator influence that also was partially restored by the ONOO(-) scavengers urate and ebselen. We conclude that ONOO(-) generated by HG impairs K(v) channel function in coronary microvessels, possibly by nitrating tyrosine residues in the pore-forming region of the K(v) channel protein.

Author List

Li H, Gutterman DD, Rusch NJ, Bubolz A, Liu Y

MESH terms used to index this publication - Major topics in bold

Animals
Azoles
Coronary Vessels
Free Radical Scavengers
Glucose
Isoindoles
Male
Membrane Potentials
Microcirculation
Nitrogen
Organoselenium Compounds
Patch-Clamp Techniques
Peroxynitrous Acid
Potassium Channels, Voltage-Gated
Rats
Rats, Sprague-Dawley
Uric Acid
Vasodilation