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.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.