Endothelial small-conductance and intermediate-conductance KCa channels: An Update on Their Pharmacology and Usefulness as Cardiovascular Targets

Heike Wulff, Ralf Köhler

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

ABSTRACT:: Most cardiovascular researchers are familiar with intermediate-conductance KCa3.1 and small-conductance KCa2.3 channels because of their contribution to endothelium-derived hyperpolarization. However, to immunologists and neuroscientists, these channels are primarily known for their role in lymphocyte activation and neuronal excitability. KCa3.1 is involved in the proliferation and migration of T cells, B cells, mast cells, macrophages, fibroblasts, and dedifferentiated vascular smooth muscle cells and is, therefore, being pursued as a potential target for use in asthma, immunosuppression, and fibroproliferative disorders. In contrast, the 3 KCa2 channels (KCa2.1, KCa2.2, and KCa2.3) contribute to the neuronal medium afterhyperpolarization and, depending on the type of neuron, are involved in determining firing rates and frequencies or in regulating bursting. KCa2 activators are accordingly being studied as potential therapeutics for ataxia and epilepsy, whereas KCa2 channel inhibitors like apamin have long been known to improve learning and memory in rodents. Given this background, we review the recent discoveries of novel KCa3.1 and KCa2.3 modulators and critically assess the potential of KCa activators for the treatment of diabetes and cardiovascular diseases by improving endothelium-derived hyperpolarizations.

Original languageEnglish
JournalJournal of Cardiovascular Pharmacology
Volume61
Issue number2
Pages (from-to)102-112
DOIs
Publication statusPublished - Feb 2013

Keywords

  • KCa3.1, KCa2.3
  • action potential
  • afterhyperpolarizatin
  • blood pressure
  • endothelium-derived hyperpolarization
  • gating modulation
  • lymphocyte activation
  • small/intermediate-conductance calcium-activated K+ channel
  • Humans
  • Molecular Targeted Therapy
  • Diabetes Mellitus/drug therapy
  • Animals
  • Endothelium, Vascular/drug effects
  • Cardiovascular Diseases/drug therapy
  • Intermediate-Conductance Calcium-Activated Potassium Channels/drug effects
  • Small-Conductance Calcium-Activated Potassium Channels/drug effects
  • Drug Design
  • Biological Factors/metabolism

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