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Shaker-related voltage-gated K+ channel expression and vasomotor function in human coronary resistance arteries. Microcirculation 2018 01;25(1)

Date

11/22/2017

Pubmed ID

29161755

Pubmed Central ID

PMC5760438

DOI

10.1111/micc.12431

Scopus ID

2-s2.0-85040240704   3 Citations

Abstract

OBJECTIVES: KV channels are important regulators of vascular tone, but the identity of specific KV channels involved and their regulation in disease remain less well understood. We determined the expression of KV 1 channel subunits and their role in cAMP-mediated dilation in coronary resistance arteries from subjects with and without CAD.

METHODS: HCAs from patients with and without CAD were assessed for mRNA and protein expression of KV 1 channel subunits with molecular techniques and for vasodilator response with isolated arterial myography.

RESULTS: Assays of mRNA transcripts, membrane protein expression, and vascular cell-specific localization revealed abundant expression of KV 1.5 in vascular smooth muscle cells of non-CAD HCAs. Isoproterenol and forskolin, two distinct cAMP-mediated vasodilators, induced potent dilation of non-CAD arterioles, which was inhibited by both the general KV blocker 4-AP and the selective KV 1.5 blocker DPO-1. The cAMP-mediated dilation was reduced in CAD and was accompanied by a loss of or reduced contribution of 4-AP-sensitive KV channels.

CONCLUSIONS: KV 1.5, as a major 4-AP-sensitive KV 1 channel expressed in coronary VSMCs, mediates cAMP-mediated dilation in non-CAD arterioles. The cAMP-mediated dilation is reduced in CAD coronary arterioles, which is associated with impaired 4-AP-sensitive KV channel function.

Author List

Nishijima Y, Korishettar A, Chabowski DS, Cao S, Zheng X, Gutterman DD, Zhang DX

Authors

David D. Gutterman MD Sr Associate Director, Professor in the Medicine department at Medical College of Wisconsin
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




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

Arterioles
Cardiovascular Diseases
Case-Control Studies
Coronary Vessels
Cyclic AMP
Humans
Potassium Channels, Voltage-Gated
Protein Subunits
RNA, Messenger
Vasodilation
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a