Copyright © 2004, European Society of Cardiology
Modulation of the voltage-dependent K+ current by intracellular Mg2+ in rat aortic smooth muscle cells
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, U.K.
* Corresponding author. Tel.: +44 1225 384471; fax: +44 1225 386114. Email address: S.V.Smirnov{at}bath.ac.uk
Objective: Intracellular magnesium ions (Mg2+i) are important in the regulation of a wide range of cellular metabolic processes and modulation of a variety of ion channels. Mg2+ deficiency has been implicated in the aetiology of various cardiovascular diseases. However, potential targets and mechanisms of action of Mg2+i in the cardiovascular system remain poorly understood. We therefore investigated the effect of Mg2+i on the voltage-gated K+ (KV) channels in rat aortic myocytes (RAMs).
Methods: KV currents (IKv) were investigated in single RAMs isolated from adult Wistar rat thoracic aorta using the whole-cell patch clamp technique. Changes in the vascular reactivity were also assessed in endothelium-denuded rat aortic rings loaded with Mg2+.
Results: An increase in Mg2+i caused several significant effects on IKv: (1) slowed down kinetics of activation at high (10 mM) Mg2+; (2) caused inward rectification at positive membrane potentials; (3) shifted the voltage-dependent inactivation, but not steady-state IKv activation; (4) the effect of Mg2+i on IKv inactivation was enhanced in the presence of intracellular ATP. Selective changes in the voltage-dependent characteristics predict a significant inhibition of the whole-cell steady-state IKv ("window current"), resulting in membrane depolarisation and enhanced tissue excitability. An increased sensitivity to KCl and the inhibitors of the IKv, tetraethylammonium and 4-aminopyridine (4-AP), was observed in Mg2+-loaded aortas, confirming this hypothesis.
Conclusion: Our results demonstrate that intracellular magnesium can act as a potent modulator of the KV channel function in vascular smooth muscle cells in the physiological range of membrane potentials, representing a novel mechanism for the regulation of KV channel activity in the vasculature.
KEYWORDS Arteries; Ion channels; K-channels; Smooth muscle; Vasoconstriction
1 Present address: University Laboratory of Physiology Parks Road, Oxford OX1 3PT.
Time for primary review 24 days
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