Imipramine inhibition of TRPM‐like plasmalemmal Mg2+ transport in vascular smooth muscle cells |
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Authors: | Koichi Furukawa Tatsuaki Matsubara Shinsuke Nakayama |
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Institution: | 1. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya, Japan;2. Department of Internal Medicine, Aichi‐Gakuin University School of Dentistry, Nagoya, Japan;3. Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan |
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Abstract: | Depression is associated with vascular disease, such as myocardial infarction and stroke. Pharmacological treatments may contribute to this association. On the other hand, Mg2+ deficiency is also known to be a risk factor for the same category of diseases. In the present study, we examined the effect of imipramine on Mg2+ homeostasis in vascular smooth muscle, especially via melastatin‐type transient receptor potential (TRPM)‐like Mg2+‐permeable channels. The intracellular free Mg2+ concentration (Mg2+]i) was measured using 31P‐nuclear magnetic resonance (NMR) in porcine carotid arteries that express both TRPM6 and TRPM7, the latter being predominant. pHi and intracellular phosphorus compounds were simultaneously monitored. To rule out Na+‐dependent Mg2+ transport, and to facilitate the activity of Mg2+‐permeable channels, experiments were carried out in the absence of Na+ and Ca2+. Changing the extracellular Mg2+ concentration to 0 and 6 mM significantly decreased and increased Mg2+]i, respectively, in a time‐dependent manner. Imipramine statistically significantly attenuated both of the bi‐directional Mg2+]i changes under the Na+‐ and Ca2+‐free conditions. This inhibitory effect was comparable in influx, and much more potent in efflux to that of 2‐aminoethoxydiphenyl borate, a well‐known blocker of TRPM7, a channel that plays a major role in cellular Mg2+ homeostasis. Neither ATP]i nor pHi correlated with changes in Mg2+]i. The results indicate that imipramine suppresses Mg2+‐permeable channels presumably through a direct effect on the channel domain. This inhibitory effect appears to contribute, at least partially, to the link between antidepressants and the risk of vascular diseases. |
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Keywords: | magnesium vascular smooth muscle tricyclic antidepressants nuclear magnetic resonance melastatin‐type transient receptor potential channels |
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