Differences in K+ current components in mesenteric artery myocytes from WKY and SHR

Am J Hypertens. 2001 Sep;14(9 Pt 1):897-907. doi: 10.1016/s0895-7061(01)02145-8.

Abstract

Previous studies have documented increased K+ permeability of arterial smooth muscle in hypertension and suggested a role in altered arterial contractile function. To characterize the mechanisms responsible for these alterations, we determined the contribution of K+ current (IK) components to whole cell IK in freshly dispersed myocytes and tetraethylammonium (TEA)-induced contractile responses in mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tetraethylammonium produced a larger tonic contractile response in SHR with a lower threshold compared to WKY (ie, 0.1 v 1 mmol/L), which was due in part to the larger Ca2+ current in SHR. Whole cell IK recorded by perforated patch methods was similar at a holding potential (HP) of -60 mV (IK60), but were larger in SHR when recorded from a HP of -20 mV (IK20). The selective blocker iberiotoxin (IbTX) was used to separate the contribution of voltage- (Kv) and calcium-dependent (KCa) components of IK60. The IK60 and IK20 component inhibited by 100 nmol/L IbTX (ie, KCa) was larger in SHR than in WKY myocytes, whereas the IbTX-insensitive IK60 component (ie, Kv) was larger in WKY. In the presence of IbTX, 1 and 10 mmol/L TEA inhibited a larger fraction of IK60 in SHR myocytes compared with WKY. The activation properties of the TEA-sensitive and TEA-insensitive Kv components determined by fitting a Boltzmann activation function to the current-voltage data, exhibited both group and treatment differences in the half maximal activation voltage (V0.5). The V0.5 of the TEA-sensitive Kv component was more positive than that of the TEA-insensitive component in both groups, and values for the V0.5 of both TEA-sensitive and TEA-insensitive components were more negative in SHR than WKY. These results show that SHR myocytes have larger KCa and smaller Kv current components compared with WKY. Furthermore, SHR myocytes have a larger TEA-sensitive Kv component. These differences may contribute to the differences in TEA contractions, resting membrane potential, Ca2+ influx, and KCa current reported in hypertensive arteries.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hypertension / metabolism
  • Male
  • Mesenteric Arteries / cytology*
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocardial Contraction / drug effects
  • Potassium Channel Blockers / administration & dosage
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sensitivity and Specificity
  • Tetraethylammonium / administration & dosage

Substances

  • Calcium Channels
  • Potassium Channel Blockers
  • Potassium Channels
  • Tetraethylammonium