Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival

نویسندگان

  • Vladimir Chubanov
  • Silvia Ferioli
  • Annika Wisnowsky
  • David G Simmons
  • Christin Leitzinger
  • Claudia Einer
  • Wenke Jonas
  • Yuriy Shymkiv
  • Harald Bartsch
  • Attila Braun
  • Banu Akdogan
  • Lorenz Mittermeier
  • Ludmila Sytik
  • Friedrich Torben
  • Vindi Jurinovic
  • Emiel Pc van der Vorst
  • Christian Weber
  • Önder A Yildirim
  • Karl Sotlar
  • Annette Schürmann
  • Susanna Zierler
  • Hans Zischka
  • Alexey G Ryazanov
  • Thomas Gudermann
چکیده

Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Insight into the molecular regulation of the epithelial magnesium channel TRPM6.

PURPOSE OF REVIEW Recent studies have greatly increased our knowledge concerning the molecular mechanisms of renal magnesium handling. This review highlights the functional features of the newly identified transient receptor potential channel melastatin subtype 6 (TRPM6), which forms the gatekeeper of active magnesium reabsorption in the kidney. RECENT FINDINGS TRPM6 confines a magnesium perm...

متن کامل

Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension.

Magnesium, an essential intracellular cation, is critically involved in many biochemical reactions involved in the regulation of vascular tone and integrity. Decreased magnesium concentration has been implicated in altered vascular reactivity, endothelial dysfunction, vascular inflammation, and structural remodeling, processes important in vascular changes and target organ damage associated wit...

متن کامل

Flavaglines Stimulate Transient Receptor Potential Melastatin Type 6 (TRPM6) Channel Activity

Magnesium (Mg2+) is essential for enzymatic activity, brain function and muscle contraction. Blood Mg2+ concentrations are tightly regulated between 0.7 and 1.1 mM by Mg2+ (re)absorption in kidney and intestine. The apical entry of Mg2+ in (re)absorbing epithelial cells is mediated by the transient receptor potential melastatin type 6 (TRPM6) ion channel. Here, flavaglines are described as a no...

متن کامل

Dietary inulin in mice stimulates Mg2+ absorption and modulates TRPM6 and TRPM7 expression in large intestine and kidney.

Complex fermentable carbohydrates, such as inulin-type fructans have been shown to improve Mg2+ absorption in the hindgut and body stores. The mechanisms for this are not well understood. The newly identified transient receptor potential melastatin 6 and 7 (TRPM6 and TRPM7) channels have been shown to function in active epithelial Mg2+ transport in the apical membrane of epithelial cells, the k...

متن کامل

Decreased renal mRNA expression of TRPM6 is associated with hypomagnesemia in C57BL/6 asthmatic mice.

BACKGROUND AND OBJECTIVES Hypomagnesemia has been reported up to 40% in asthma patients, and a relationship between hypomagnesemia and asthma severity has been previously characterized. However, the mechanism for hypomagnesemia in asthma patients is not clear. Transient receptor potential melastatin 6 (TRPM6) is a newly identified channel that is involved in active epithelial magnesium transpor...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2016