Shaker-related voltage-gated K+ channel expression and vasomotor function in human coronary resistance arteries. Microcirculation 2018 Jan;25(1)
Date
11/22/2017Pubmed ID
29161755Pubmed Central ID
PMC5760438DOI
10.1111/micc.12431Scopus ID
2-s2.0-85040240704 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
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 DXAuthor
David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ArteriolesCardiovascular Diseases
Case-Control Studies
Coronary Vessels
Cyclic AMP
Humans
Potassium Channels, Voltage-Gated
Protein Subunits
RNA, Messenger
Vasodilation