Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text PDF (Full Text) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jiang, J. Articles by Yue, L. Search for Related Content PubMed PubMed Citation Articles by Jiang, J. Articles by Yue, L. Social Bookmarking                      What's this?

Center for Cardiology and Cardiovascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06032

Correspondence to Lixia Yue: lyue{at}uchc.edu

TRPM7 is unique in being both an ion channel and a protein kinase. It conducts a large outward current at +100 mV but a small inward current at voltages ranging from –100 to –40 mV under physiological ionic conditions. Here we show that the small inward current of TRPM7 was dramatically enhanced by a decrease in extracellular pH, with an 10-fold increase at pH 4.0 and 1–2-fold increase at pH 6.0. Several lines of evidence suggest that protons enhance TRPM7 inward currents by competing with Ca²⁺ and Mg²⁺ for binding sites, thereby releasing blockade of divalent cations on inward monovalent currents. First, extracellular protons significantly increased monovalent cation permeability. Second, higher proton concentrations were required to induce 50% of maximal increase in TRPM7 currents when the external Ca²⁺ and Mg²⁺ concentrations were increased. Third, the apparent affinity for Ca²⁺ and Mg²⁺ was significantly diminished at elevated external H⁺ concentrations. Fourth, the anomalous-mole fraction behavior of H⁺ permeation further suggests that protons compete with divalent cations for binding sites in the TRPM7 pore. Taken together, it appears that at physiological pH (7.4), Ca²⁺ and Mg²⁺ bind to TRPM7 and inhibit the monovalent cationic currents; whereas at high H⁺ concentrations, the affinity of TRPM7 for Ca²⁺ and Mg²⁺ is decreased, thereby allowing monovalent cations to pass through TRPM7. Furthermore, we showed that the endogenous TRPM7-like current, which is known as Mg²⁺-inhibitable cation current (MIC) or Mg nucleotide–regulated metal ion current (MagNuM) in rat basophilic leukemia (RBL) cells was also significantly potentiated by acidic pH, suggesting that MIC/MagNuM is encoded by TRPM7. The pH sensitivity represents a novel feature of TRPM7 and implies that TRPM7 may play a role under acidic pathological conditions.

M. Li's present address is Renmin Hospital of Wuhan University, People's Republic of China.

Abbreviations used in this paper: DVF, divalent-free solution; MagNuM, Mg nucleotide–regulated metal ion current; MIC, Mg²⁺-inhibitable cation; RBL, rat basophilic leukemia; TRPM, melastatin-related transient receptor potential.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Brauchi, G. Krapivinsky, L. Krapivinsky, and D. E. Clapham TRPM7 facilitates cholinergic vesicle fusion with the plasma membrane PNAS, June 17, 2008; 105(24): 8304 - 8308. [Abstract] [Full Text] [PDF]

				T. Numata and Y. Okada Proton Conductivity through the Human TRPM7 Channel and Its Molecular Determinants J. Biol. Chem., May 30, 2008; 283(22): 15097 - 15103. [Abstract] [Full Text] [PDF]

				R. M. Touyz Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1103 - H1118. [Abstract] [Full Text] [PDF]

				M. Semtner, M. Schaefer, O. Pinkenburg, and T. D. Plant Potentiation of TRPC5 by Protons J. Biol. Chem., November 16, 2007; 282(46): 33868 - 33878. [Abstract] [Full Text] [PDF]

				J. Jiang, M.-H. Li, K. Inoue, X.-P. Chu, J. Seeds, and Z.-G. Xiong Transient Receptor Potential Melastatin 7 like Current in Human Head and Neck Carcinoma Cells: Role in Cell Proliferation Cancer Res., November 15, 2007; 67(22): 10929 - 10938. [Abstract] [Full Text] [PDF]

				M. Li, J. Du, J. Jiang, W. Ratzan, L.-T. Su, L. W. Runnels, and L. Yue Molecular Determinants of Mg2+ and Ca2+ Permeability and pH Sensitivity in TRPM6 and TRPM7 J. Biol. Chem., August 31, 2007; 282(35): 25817 - 25830. [Abstract] [Full Text] [PDF]

				B. F. Bessac and A. Fleig TRPM7 channel is sensitive to osmotic gradients in human kidney cells J. Physiol., August 1, 2007; 582(3): 1073 - 1086. [Abstract] [Full Text] [PDF]

				V. Chubanov, K. P. Schlingmann, J. Waring, J. Heinzinger, S. Kaske, S. Waldegger, M. M. y Schnitzler, and T. Gudermann Hypomagnesemia with Secondary Hypocalcemia due to a Missense Mutation in the Putative Pore-forming Region of TRPM6 J. Biol. Chem., March 9, 2007; 282(10): 7656 - 7667. [Abstract] [Full Text] [PDF]

				M. Li, J. Jiang, and L. Yue Functional Characterization of Homo- and Heteromeric Channel Kinases TRPM6 and TRPM7 J. Gen. Physiol., April 24, 2006; 127(5): 525 - 537. [Abstract] [Full Text] [PDF]

				L.-T. Su, M. A. Agapito, M. Li, W. T. N. Simonson, A. Huttenlocher, R. Habas, L. Yue, and L. W. Runnels TRPM7 Regulates Cell Adhesion by Controlling the Calcium-dependent Protease Calpain J. Biol. Chem., April 21, 2006; 281(16): 11260 - 11270. [Abstract] [Full Text] [PDF]

				P. Demeuse, R. Penner, and A. Fleig TRPM7 Channel Is Regulated by Magnesium Nucleotides via its Kinase Domain J. Gen. Physiol., March 27, 2006; 127(4): 421 - 434. [Abstract] [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents