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.
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