TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon

Area of Science:

• Cell Biology
• Molecular Physiology
• Gastroenterology

Background:

• Intestinal magnesium (Mg) uptake is crucial for maintaining systemic Mg balance.
• Colon cells express homologous transient receptor potential melastatin type (TRPM) 6 and 7 Mg²⁺ channels, but their specific roles and interactions remain unclear.

Purpose of the Study:

• To investigate the functional roles of TRPM6 and TRPM7 channels in human colon cells.
• To elucidate the consequences of TRPM6 and TRPM7 channel interactions on Mg²⁺ influx, cell proliferation, and migration.

Main Methods:

• Utilized human colon cell lines expressing both TRPM6 and TRPM7.
• Performed genetic knockdown of TRPM6 or TRPM7 using RNA interference.
• Applied pharmacological inhibition using NS8593, a specific TRPM6/7 inhibitor, with and without Mg supplementation.

Main Results:

• TRPM7 silencing led to increased Mg²⁺ influx, enhanced cell proliferation, and migration.
• TRPM6 downregulation did not significantly alter Mg²⁺ influx or cell proliferation.
• TRPM6/7 inhibition by NS8593 reduced Mg²⁺ influx, proliferation, and migration, effects reversed by Mg supplementation.

Conclusions:

• TRPM7 and TRPM6 form functional Mg²⁺ channels, potentially as homomers and heteromers, in colon cells.
• The expression ratio of TRPM6 and TRPM7 influences channel function.
• TRPM6/7 complexes and their mediated Mg²⁺ influx are essential for human colon epithelial cells, with TRPM6 being non-redundant.