Vasocontrictive and Vasodilatative Effects of Transient Receptor Potential Melastatin‐4 (TRPM4) Modulation

Abstract

TRPM4 is activated by the elevation of intracellular Ca2+-concentration, and it is permeable to Na+- and K+-ions when activated. It is considered to participate in pressure-induced membrane depolarization and vasoconstriction (basal myogenic tone). Our aim was to investigate the role of TRPM4 in arteriolar diameter regulation. Experiments were performed on MOVAS cells, skeletal muscle and mesenteric arteries, human saphenic veins, and in an in vivo measurement system. In vivo experiments were performed on male Wistar-Kyoto (WKY) rats and blood pressure was measured via carotid artery canule. The TRPM4 antagonist 9-Phenanthrol caused a transient decrease in blood pressure. In experiments performed under isometric conditions human saphenic veins were used that remained after coronary bypass surgery. After preconstriction with 10µM norepinephrine the TRPM4 antagonist decreased the contractile force of the vessel ring by 67,1±20,9%. On MOVAS cells the intracellular Ca2+-concentration could be measured, and the supposed TRPM4 activator A23187 caused elevation of intracellular Ca2+-concentration (1µM A23187 caused the elevation of 340/380 ratio from 0,71±0,05 to 0,81±0,04, p<0,05). Our data confirms that TRPM4 may have a major role in vascular smooth muscle contraction. Possibly, the activation of the receptor causes membrane depolarization and that results in the opening of the voltage dependent Ca2+-channels, which increases intracellular Ca2+-concentration and leads to contraction.