Publication Date

2019

Document Type

Thesis

Committee Members

J. Ashot Kozak, Ph.D. (Advisor); Mauricio Di Fulvio, Ph.D. (Committee Member); Kathrin L. Engisch, Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Magnesium is an important divalent metal cation that is involved in numerous cellular functions. The details of cellular Mg2+ regulation, homeostasis and transport remain unclear. Magnesium transporter protein (MagT1) is a Mg2+ transporter and deficiency of this protein has been reported to lead to impaired Mg2+ influx and a decreased cytoplasmic [Mg2+]. Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed membrane protein containing a channel pore and a C-terminal alpha-type serine/threonine protein kinase domain. Importantly, TRPM7 channel is believed to conduct both Mg2+ and Ca2+. In the present study, we investigated if TRPM7 can be used as a bioassay of internal and external Mg2+ in Jurkat T cells. We have investigated the long term effects of Mg2+ changes on TRPM7 channel activity. Under physiological conditions, cytoplasmic Mg2+ concentrations of 0.1 – 0.3 mM are sufficient to inhibit the majority of TRPM7 channels. Extracellular Mg2+ blocks inward TRPM7 currents carried by monovalent cations. When the cytoplasmic Mg2+ concentration is reduced, TRPM7 channels open and produce an outwardly-rectifying current. We find that the extent of TRPM7 current activation can be used effectively to estimate changes of cytoplasmic Mg2+ concentration. Our findings can be extended to cell types other than Jurkat T cells.

Page Count

103

Department or Program

Department of Neuroscience, Cell Biology, and Physiology

Year Degree Awarded

2019


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