腎尿細管・血管平滑筋特異的TRPM6/7機能抑制マウスの心血管機能特性

• Published in: 日本薬理学会年会要旨集 p. 3-O-092
• Main Authors: 田頭, 秀章, 喜多, 知, 根本, 隆行, 沼田, 朋大, 喜多, 紗斗美, 岩本, 隆宏
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2020
• Subjects: hypotension; magnesium
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.93.0_3-O-092

Magnesium ion (Mg2+) is an essential divalent cation and cellular Mg2+ concentration is tightly regulated by various Mg2+ channels/transporters. Therefore, dysfunction of Mg2+ channels/transporters may lead to a variety of cardiovascular or neuromuscular disorders. TRPM7 is a non-selective cation channel, which predominantly permeates Mg2+ under physiological conditions. We generated tissue-specific transgenic mouse models expressing the dominant negative TRPM7 mutant (TRPM7DN-Tg) to study the physiological and pathophysiological mechanisms of Mg2+ regulation. Whole-cell patch-clamp recordings revealed that TRPM6/7 currents in HEK293 cells were almost completely attenuated by co-expression of TRPM7DN mutant. Renal tubule-specific TRPM7DN-Tg exhibited dysregulation of serum Mg2+ level and urinary Mg2+ excretion. Interestingly, in these mice, phenylephrine (PE)-induced vascular contractile responses was significantly attenuated. On the other hand, vascular smooth muscle-specific TRPM7DN-Tg showed attenuation of PE-induced contractile responses without changing serum Mg2+ level and urinary Mg2+ excretion. These results suggest that TRPM6/7 channels are tissue-dependently involved in the regulation of Mg2+ homeostasis and vascular contraction. Our tissue-specific TRPM7DN-Tg will be useful animal models for studying magnesium disorders.