Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches

Pharmacol Res. 2013 Apr;70(1):126-38. doi: 10.1016/j.phrs.2013.01.008. Epub 2013 Jan 31.


Ion channels are multimeric, transmembrane proteins that selectively mediate ion flux across the plasma membrane in a variety of cells including vascular smooth muscle cells (VSMCs). The dynamic interplay of Ca(2+) and K(+) channels on the plasma membrane of VSMCs plays a pivotal role in modulating the vascular tone of small arteries and arterioles. The abnormally-elevated arterial tone observed in hypertension thus points to an aberrant expression and function of Ca(2+) and K(+) channels in the VSMCs. In this short review, we focus on the three well-studied ion channels in VSMCs, namely the L-type Ca(2+) (CaV1.2) channels, the voltage-gated K(+) (KV) channels, and the large-conductance Ca(2+)-activated K(+) (BK) channels. First, we provide a brief overview on the physiological role of vascular CaV1.2, KV and BK channels in regulating arterial tone. Second, we discuss the current understanding of the expression changes and regulation of CaV1.2, KV and BK channels in the vasculature during hypertension. Third, based on available proof-of-concept studies, we describe the potential therapeutic approaches targeting these vascular ion channels in order to restore blood pressure to normotensive levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / metabolism*
  • Ion Channel Gating / drug effects
  • Molecular Targeted Therapy
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Protein Subunits


  • Antihypertensive Agents
  • Calcium Channels
  • Potassium Channels
  • Protein Subunits