Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease

Expert Opin Ther Targets. 2010 Feb;14(2):143-55. doi: 10.1517/14728220903540257.


Importance of the field: Cardiovascular disease is a leading cause of death in modern societies. Hyperpolarizing Ca(2+)-activated K(+) channels (K(Ca)) are important membrane proteins in the control of arterial tone and pathological vascular remodelling and thus could serve as new drug targets.

Areas covered in this review: We summarize recent advances in the field of vascular K(Ca) and their roles in cardiovascular pathologies such as hypertension and restenosis disease and draw attention to novel small-molecule channel modulators and their possible therapeutic utility. This review focuses on literature from the last four to five years.

What the reader will gain: Pharmacological opening of endothelial KCa3.1/KCa2.3 channels stimulates endothelium-derived-hyperpolarizing-factor-mediated arteriolar dilation and lowers blood pressure. Inhibition of smooth muscle KCa3.1 channels has beneficial effects in restenosis disease and atherosclerosis. We consider the therapeutic potential of KCa3.1/KCa2.3 openers as novel endothelium-specific antihypertensive drugs as well as of KCa3.1-blockers for the treatment of pathological vascular remodelling and discuss advantages and disadvantages of the pharmacotherapeutic approaches.

Take home message: Pharmacological manipulation of vascular K(Ca) channels by novel small-molecule modulators offers new venues for alternative treatments of hypertension, restenosis and atherosclerosis. Additional efforts are required to optimize these compounds and to validate them as cardiovascular-protective drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy*
  • Biological Factors / physiology
  • Endothelium, Vascular / physiology
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / etiology
  • Intermediate-Conductance Calcium-Activated Potassium Channels / drug effects
  • Intermediate-Conductance Calcium-Activated Potassium Channels / physiology
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / drug effects
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / physiology
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors
  • Potassium Channels, Calcium-Activated / drug effects*
  • Potassium Channels, Calcium-Activated / physiology
  • Vascular Diseases / drug therapy*
  • Vasodilation


  • Biological Factors
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • KCNMA1 protein, human
  • KCNN4 protein, human
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Potassium Channels, Calcium-Activated
  • endothelium-dependent hyperpolarization factor