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Articles in PresS, published online ahead of print October 24, 2001
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00382.2001
Submitted on May 8, 2001
Accepted on October 15, 2001
1 Pharmacology & Toxicology, Medical College of Georgia, Augusta, GA, USA
2 Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA
3 Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA
* To whom correspondence should be addressed. E-mail: rwhite{at}mail.mcg.edu.
The insulin resistance (IR) syndrome is associated with impaired vascular relaxation; however, the underlying pathophysiology is unknown. Potassium channel activation causes vascular smooth muscle hyperpolarization and relaxation. The present study determined if a reduction in large conductance, calcium- and voltage-activated potassium (BKCa) channel activity contributes to an impaired vascular relaxation in IR rats. BKCa channels were characterized in mesenteric microvessels from IR and control rats. Macroscopic current density was reduced in myocytes from IR animals compared to controls. In addition, inhibition of BKCa channels with tetraethylammonium (1mM) or iberiotoxin (100nM) was greater in myocytes from control (70%) compared to IR animals (~20%). Furthermore, activation of BKCa channels with NS1619 was 3-times more effective at increasing outward current in cells from control vs. IR animals. Single-channel and Western blot analysis of BKCa channels revealed similar conductance, amplitude, voltage- and Ca2+-sensitivity, and expression density between the two groups. These data provide the first direct evidence that microvascular potassium currents are reduced in IR, and suggest a molecular mechanism that could account for impaired vascular relaxation in IR.
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