Up-Regulation of the Voltage-Gated K V 2.1 K + Channel in the Renal Arterial Myocytes of Dahl Salt-Sensitive Hypertensive Rats

Biol Pharm Bull. 2017;40(9):1468-1474. doi: 10.1248/bpb.b17-00289.

Abstract

Salt-sensitive hypertension induces renal injury via decreased blood flow in the renal artery (RA), and ion channel dysfunction in RA myocytes (RAMs) may be involved in the higher renal vascular resistance. We examined the effects of several voltage-gated K+ (KV) channel blockers on the resting tension in endothelium-denuded RA strips and delayed-rectifier K+ currents in RAMs of Dahl salt-sensitive hypertensive rats (Dahl-S) fed with low- (Dahl-LS) and high-salt diets (Dahl-HS). The tetraethylammonium (TEA)-induced contraction in RA strips were significantly larger in Dahl-HS than Dahl-LS. Correspondingly, TEA-sensitive KV currents were significantly larger in the RAMs of Dahl-HS than Dahl-LS. Among the TEA-sensitive KV channel subtypes, the expression levels of KV2.1 transcript and protein were significantly higher in the RA of Dahl-HS than Dahl-LS, while those of KV1.5, KV7.1, and KV7.4 transcripts was comparable in two groups. KV2.1 currents detected as the guangxitoxin-1E-sensitive component were larger in the RAMs of Dahl-HS than Dahl-LS. These suggest that the up-regulation of the KV2.1 channel in RAMs may be involved in the compensatory mechanisms against decreased renal blood flow in salt-sensitive hypertension.

Keywords: Dahl rat; KV2.1; renal artery; salt-sensitive hypertension; voltage-gated K+ (KV) channel.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Delayed Rectifier Potassium Channels / drug effects
  • Endothelium, Vascular / drug effects
  • Hypertrophy, Left Ventricular / pathology
  • Male
  • Muscle Contraction / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Organ Size
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Inbred Dahl
  • Renal Artery / cytology
  • Renal Artery / metabolism*
  • Shab Potassium Channels / antagonists & inhibitors
  • Shab Potassium Channels / biosynthesis*
  • Tetraethylammonium / pharmacology
  • Up-Regulation / drug effects

Substances

  • Delayed Rectifier Potassium Channels
  • Kcnb1 protein, rat
  • Potassium Channel Blockers
  • Shab Potassium Channels
  • Tetraethylammonium