Faculty Collaboration Database

High glucose impairs voltage-gated K(+) channel current in rat small coronary arteries. Circ Res 2001 Jul 20;89(2):146-52

Date

07/21/2001

Pubmed ID

11463721

DOI

10.1161/hh1401.093294

Scopus ID

2-s2.0-0035920260 (requires institutional sign-in at Scopus site)   128 Citations

Abstract

Hyperglycemia is associated with impaired endothelium-dependent dilation that is due to quenching of NO by superoxide (O(2)(. -)). In small coronary arteries (CAs), dilation depends more on smooth muscle hyperpolarization, such as that mediated by voltage-gated K(+) (Kv) channels. We determined whether high glucose enhances O(2)(.-) production and reduces microvascular Kv channel current and functional responses. CAs from Sprague-Dawley rats were incubated 24 hours in medium containing either normal glucose (NG, 5.5 mmol/L D-glucose), high glucose (HG, 23 mmol/L D-glucose), or L-glucose (LG, 5.5 mmol/L D-glucose and 17 mmol/L L-glucose). O(2)(.-) production was increased in HG arteries. Whole-cell patch clamping showed a reduction of 4-aminopyridine (4-AP)-sensitive current (Kv current) from smooth muscle cells of HG CAs versus NG CAs or versus LG CAs (peak density was 9.95+/-5.3 pA/pF for HG versus 27.8+/-6.8 pA/pF for NG and 28.5+/-5.2 pA/pF for LG; P<0.05). O(2)(.-) generation (xanthine+xanthine oxidase) decreased K(+) current density, with no further reduction by 4-AP. Partial restoration was observed with superoxide dismutase and catalase. Constriction to 3 mmol/L 4-AP was reduced in vessels exposed to HG (13+/-5%, P<0.05) versus NG (30+/-7%) or LG (34+/-4%). Responses to KCl and nifedipine were not different among groups. Superoxide dismutase and catalase increased contraction to 4-AP in HG CAs. This is the first direct evidence that exposure of CAs to HG impairs Kv channel activity. We speculate that this O(2)(.-)-induced impairment may reduce vasodilator responsiveness in the coronary circulation of subjects with coronary disease or its risk factors.

Author List

Liu Y, Terata K, Rusch NJ, Gutterman DD

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

4-Aminopyridine
Analysis of Variance
Animals
Antioxidants
Catalase
Coronary Vessels
Dose-Response Relationship, Drug
Electrophysiology
Fluorescence
Glucose
In Vitro Techniques
Ion Channel Gating
Male
Membrane Potentials
Microscopy, Video
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Potassium Channels
Rats
Rats, Sprague-Dawley
Superoxide Dismutase
Superoxides
Vasoconstriction