Recent work by the author has shown that the sensitivity of the Na-K ATPase and Na-K pump of human red blood cells to inhibition by Ca is increased 20 fold by an unidentified protein present in the cytoplasm of red cells. The protein is not calmodulin, appears to bind to the membrane of human red cells in a Ca-dependent manner and increases the sensitivity of the Na-K ATpase to the extent that 50% inhibition occur at low micromolar concentrations of free Ca. If this protein also alters the effect of Ca on the Na-K ATPase in other cells, then it could play a fundamental role in cellular regulation of the Na-K ATPase in other cells, then it could play a fundamental role in cellular regulation of the Na-K pump under many conditions. For instance, it could be involved in the relationship between the Na-K pump and the Na/Ca exchange and the control of free Ca in smooth muscle which may underlie the inotropic effect of cardiac glycosides and the relationship between sodium metabolism and hypertension.
The first aim of the proposed project is to purify and identify the protein; the second is to determine its molecular weight, amino acid composition, end terminals, and possible prosthetic groups.
The third aim i s to study the effect of the purified protein on Ca inhibition of the Na-K ATPase in human red cell membranes and the fourth is to establish the effect on the purified Na-K ATPase in human red cell membranes and the fourth is to establish the effect on the purified Na-K ATPase. The fifth and final aim is to investigate if the Na-K ATPase in patients with essential hypertension are more sensitive than normal to inhibition by Ca and to establish what role the purified protein may play in such differences.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032223-02
Application #
3280853
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1984-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Yang, Y C; Yingst, D R (1989) Effects of intracellular free Ca and rate of Ca influx on the Ca pump. Am J Physiol 256:C1138-44
Yingst, D R; Polasek, P M (1985) Sensitivity and reversibility of Ca-dependent inhibition of the (Na+ + K+)-ATPase of human red blood cells. Biochim Biophys Acta 813:282-6