Key result
High glucose impairs Kv channels in rat coronary microvessels via peroxynitrite-mediated tyrosine nitration.
Why the study?
Does high glucose exposure impair voltage-gated K+ channel function via peroxynitrite-mediated nitration in rat coronary microvessels?
Does high glucose exposure impair voltage-gated K+ channel function via peroxynitrite-mediated nitration in rat coronary microvessels?
High glucose impairs voltage-gated K+ channel function in coronary microvessels via peroxynitrite-mediated nitration, providing a potential mechanism for diabetic vascular dysfunction.
May link hyperglycemia to coronary dysfunction in diabetes; hypothesis-generating with no immediate clinical implications.
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.
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Li et al. (2004) studied this question. High glucose vs. Normal glucose (5.5 mmol/l) was evaluated on Nitration and impairment of Kv channels. Exposure to high glucose for 24 hours impaired voltage-gated K+ channel function in rat coronary microvessels, likely via peroxynitrite-mediated nitration of tyrosine residues.