Premium
Impaired forskolin‐mediated dilation in coronary arterioles of hypercholesterolemic swine: role of voltage‐dependent K + channels
Author(s) -
Heaps Cristine L.,
Jeffery Elise C.,
Price Elmer M.,
Bowles Doug K.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a846-c
Subject(s) - forskolin , tetraethylammonium , medicine , endocrinology , gene isoform , adenosine , chemistry , biochemistry , gene , receptor , potassium , organic chemistry
We previously reported that coronary arterioles from hypercholesterolemic (HC) swine display attenuated adenosine‐mediated dilation which is attributable to a reduced contribution of tetraethylammonium (TEA)‐sensitive voltage‐dependent K + (Kv) channels. For this study, we hypothesized that hypercholesterolemia attenuates the expression and/or function of highly‐TEA sensitive Kv channel isoforms, Kv1.1 and the Kv3 subfamily. Pigs were randomly assigned to a control or high fat/high cholesterol diet for 20–22 wks, sacrificed, and arterioles (~125 μm) isolated from the left‐ventricular free wall. Forskolin‐mediated dilation was significantly attenuated in a concentration‐dependent manner by TEA in pressurized arterioles of control but not HC animals. However, selective inhibitors of Kv1.1 and Kv3.4 isoforms did not alter forskolin‐mediated dilation or whole‐cell Kv current in arterioles from control or HC pigs. Quantitative RT‐PCR revealed similar expression levels of Kv3.1 and 3.3 with undetectable expression of Kv1.1, 3.2 and 3.4. Thus, while highly TEA‐sensitive Kv channels contribute to forskolin‐mediated dilation in control but not HC swine, mRNA expression of these channels is not altered by HC. Taken together, these results suggest that the attenuated relaxation is attributable to impaired coupling of forskolin with a highly TEA‐sensitive Kv channel isoform(s). Support: AHA 0330252N