Validation of a Rb+ uptake assay for the mouse embryonic stem cell-derived cardiomyocytes Na+, K+ ATPase.
Human Na+, K+ ATPase, an ATP-driven ion transporter, is an emerging drug target for heart-related conditions. Three types of assays including purified enzyme, radiotracer flux, and cold Rb+ flux have been used to determine the activity of this transporter. As an alternative to primary cardiomyocytes, mouse embryonic stem cells-derived cardiomyocytes with functional expression of essential cardiac ion channels were used in the present studies. The results on its pharmacology with digitoxin and ouabain, the 2 well-known cardioglycosides, imply that these cardiomyocytes can be used as a predictive model for the identification of modulators of Na+, K+ ATPase in HTS format.
Gill
Sikander
S
Department of R&D, Aurora Biomed Inc., 1001 E. Pender Street, Vancouver, BC V6A1W2, Canada. gill@aurorabiomed.com
Gill
Rajwant
R
Liang
Sophia
S
D000818:Animals; D002478:Cells, Cultured; D004074:Digitoxin / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D012413:Rubidium / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*
D010042:Ouabain; D004074:Digitoxin; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium