Potassium (BK(Ca)) currents are reduced in microvascular smooth muscle cells from insulin-resistant rats.
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 whether a reduction in large conductance calcium- and voltage-activated potassium (BK(Ca)) channel activity contributes to impaired vascular relaxation in IR rats. BK(Ca) channels were characterized in mesenteric microvessels from IR and control rats. Macroscopic current density was reduced in myocytes from IR animals compared with controls. In addition, inhibition of BK(Ca) channels with tetraethylammonium (1 mM) or iberiotoxin (100 nM) was greater in myocytes from control (70%) compared with IR animals (approximately 20%). Furthermore, activation of BK(Ca) channels with NS-1619 was three times more effective at increasing outward current in cells from control versus IR animals. Single channel and Western blot analysis of BK(Ca) channels revealed similar conductance, amplitude, voltage sensitivity, 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.
Dimitropoulou
Christiana
C
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, Georgia 30912-2300, USA. cdimitro@mail.mcg.edu
Han
Guichun
G
Miller
Allison W
AW
Molero
Mariela
M
Fuchs
Leslie C
LC
White
Richard E
RE
Carrier
Gerald O
GO
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D005632:Fructose / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology
D004040:Dietary Carbohydrates; D007328:Insulin; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D021122:Protein Subunits; D005632:Fructose; D019789:Tetraethylammonium