Poster Presentation 2014 International Biophysics Congress

Extracellular acidosis induces a TRPM7-like sodium current in mouse distal convoluted tubule (MDCT) cells  (#579)

Corey Valinsky 1 , Rhian Touyz 2 , Alvin Shrier 1
  1. Department of Physiology, McGill University, Montreal, Quebec, Canada
  2. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland

Previous studies have demonstrated the presence of a TRPV5/TRPV6 current responsible for calcium transport in mouse distal convoluted tubule (MDCT) cells. It was also suggested that TRPM6 and TRPM7, both non-selective cation channels permeant to magnesium under neutral pH and sodium under acidic pH, are also present in these cells but their relative expression and functional contributions are unknown. Our results demonstrate that the level of expression of mRNA transcripts for TRPM7 in MDCT cells is one hundred and twenty five fold greater than that for TRPM6. Using whole-cell patch-clamp, we identified a non-selective cation current that was induced by acidic extracellular solutions. We found that only this low pH (pH 5) induced current was blocked by the specific TRPM7 inhibitor, FTY720, and reduced by TRPM7-siRNA. To rule out the presence of a significant TRPM6 current, we used 200µM 2-APB that is known to enhance TRPM6 but block TRPM7. We observed a block of current by 2-APB at all pH values tested, including pH 5.0, consistent with the presence of a TRPM7-like current and the absence of a significant TRPM6 current. Ion permeation experiments revealed that calcium and sodium permeated these cells at pH 7.4 and 6.5, but not magnesium, further supporting the notion that TRPM7 is not functionally present in these cells under neutral pH. Most relevant was our finding that the low pH induced current only permeated sodium, once again consistent with the behaviour of TRPM7. Thus, our results suggest that reducing the extracellular pH from 7.4 to 5 results in the induction of a TRPM7-like sodium current in MDCT cells.