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Modulation of the voltage-dependent K+ current by intracellular Mg2+ in rat aortic smooth muscle cells

Paolo Tammaro1, Amy L Smith, Barry L Crowley

  • 1Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, U.K.

Cardiovascular Research
|January 11, 2005
PubMed
Abstract

Insights

Intracellular magnesium ions (Mg2+i) regulate voltage-gated potassium (KV) channels in rat aortic cells. This finding reveals a new mechanism for controlling vascular excitability and cardiovascular health.

Area of Science:

  • Cardiovascular Physiology
  • Cellular Electrophysiology
  • Ion Channel Modulation

Background:

  • Intracellular magnesium ions (Mg2+i) are crucial for cellular metabolism and ion channel function.
  • Mg2+ deficiency is linked to cardiovascular diseases, but its specific roles in the vasculature are unclear.
  • Voltage-gated potassium (KV) channels are key regulators of vascular smooth muscle cell excitability.

Purpose of the Study:

  • To investigate the effects of intracellular Mg2+ on KV channels in rat aortic myocytes (RAMs).
  • To explore the potential mechanisms by which Mg2+ influences vascular function.

Main Methods:

  • Whole-cell patch clamp electrophysiology was used to record KV currents (IKv) in isolated RAMs.
  • Vascular reactivity was assessed in rat aortic rings loaded with Mg2+.

Main Results:

  • Increased Mg2+i altered KV channel kinetics, including slowed activation and inward rectification.
  • Mg2+i shifted voltage-dependent inactivation of KV channels, enhanced by intracellular ATP.
  • These changes predict inhibition of the KV "window current," leading to membrane depolarization and increased tissue excitability.
  • Mg2+-loaded aortas showed increased sensitivity to KCl and KV channel inhibitors.

Conclusions:

  • Intracellular magnesium significantly modulates KV channel function in vascular smooth muscle cells.
  • This represents a novel mechanism for regulating vascular activity and excitability.
  • Understanding Mg2+ modulation of KV channels offers insights into cardiovascular disease mechanisms.

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