Modulation of the voltage-dependent K + current by intracellular Mg 2+ in rat aortic smooth muscle cells

25Citations
Citations of this article
10Readers
Mendeley users who have this article in their library.

Abstract

Intracellular magnesium ions (Mg 2+i) are important in the regulation of a wide range of cellular metabolic processes and modulation of a variety of ion channels. Mg 2+ deficiency has been implicated in the aetiology of various cardiovascular diseases. However, potential targets and mechanisms of action of Mg 2+i in the cardiovascular system remain poorly understood. We therefore investigated the effect of Mg 2+i on the voltage-gated K + (K V) channels in rat aortic myocytes (RAMs). K V currents (I Kv) 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 Mg 2+. An increase in Mg 2+i caused several significant effects on I Kv: (1) slowed down kinetics of activation at high (10 mM) Mg 2+; (2) caused inward rectification at positive membrane potentials; (3) shifted the voltage-dependent inactivation, but not steady-state I Kv activation; (4) the effect of Mg 2+i on I Kv 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 I Kv ("window current"), resulting in membrane depolarisation and enhanced tissue excitability. An increased sensitivity to KCl and the inhibitors of the I Kv, tetraethylammonium and 4-aminopyridine (4-AP), was observed in Mg 2+-loaded aortas, confirming this hypothesis. Our results demonstrate that intracellular magnesium can act as a potent modulator of the K V channel function in vascular smooth muscle cells in the physiological range of membrane potentials, representing a novel mechanism for the regulation of K V channel activity in the vasculature. © 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Cite

CITATION STYLE

APA

Tammaro, P., Smith, A. L., Crowley, B. L., & Smirnov, S. V. (2005). Modulation of the voltage-dependent K + current by intracellular Mg 2+ in rat aortic smooth muscle cells. Cardiovascular Research, 65(2), 387–396. https://doi.org/10.1016/j.cardiores.2004.10.035

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free