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Inward rectifiers and their regulation by endogenous polyamines.

Victoria A Baronas1, Harley T Kurata1

  • 1Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia Vancouver, BC, Canada.

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|September 16, 2014
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Summary

Polyamines block strongly rectifying inwardly-rectifying potassium (Kir) channels, regulating cell electrical activity. This review details polyamine block mechanisms and the physiological roles of these Kir channels.

Keywords:
channelopathyinward rectifierion channel blockpolyaminespotassium channelsvoltage-dependent gating

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Area of Science:

  • Molecular biology
  • Biophysics
  • Physiology

Background:

  • Inwardly-rectifying potassium (Kir) channels are crucial for maintaining resting membrane potential and regulating cellular electrical excitability.
  • Strongly rectifying Kir channels display steep voltage dependence, ceasing activity at depolarized potentials.
  • This voltage dependence is primarily mediated by blockade from endogenous polyamines.

Purpose of the Study:

  • To summarize current knowledge on the molecular mechanisms of polyamine block in Kir channels.
  • To provide perspective on unresolved questions regarding this ion channel blockade mechanism.
  • To briefly review the physiological roles of polyamine-sensitive, strongly rectifying Kir channels, particularly the Kir2 family.

Main Methods:

  • Literature review of structure-function studies on Kir channels and polyamine interactions.
  • Analysis of existing data on polyamine binding sites and ion displacement within the Kir channel pore.
  • Synthesis of information on channelopathies linked to altered polyamine sensitivity.

Main Results:

  • Polyamines enter the intracellular side of the Kir channel pore, displacing ions to bind in the transmembrane region.
  • Specific structural elements of Kir channels dictate their susceptibility to polyamine block and the steep voltage dependence.
  • Alterations in polyamine sensitivity or activity of these channels are associated with various channelopathies.

Conclusions:

  • Polyamine block is a key mechanism controlling the function of strongly rectifying Kir channels.
  • Understanding polyamine-Kir channel interactions is vital for comprehending cellular electrophysiology and associated diseases.
  • Further research is needed to address lingering uncertainties in the molecular mechanisms of polyamine block.