Principles of regulation in P-type ion pumps. Implications for cardiac function.

P-type ATPases (pumps) are membrane enzymes that play a key role in cellular ion house-keeping. Well-known representatives of this family are the Na+K+ATPase and the SERCA and SPCA Ca2+ ATPases. The transmembrane ion gradients generated by these pumps are of vital importance for amongst others the normal heart function. Hence, both the Na+K+ATPase and the SERCA pumps are important therapeutic targets for heart failure. This research aims to further explore the general principles underlying the mechanisms controlling the affinity of the pumps for their respective transported substrates. N- and C-terminal segments of these ATPases (amongst which in particular the C-terminus of SERCA2b) or functionally-related extrinsic regulatory proteins (phospholamban, beta and gamma sub units of Na+K+ATPase) act as affinity modulators. Understanding the relevant mechanisms and principles may lead to the development of pump-specific pharmacotherapy for heart failure.

Keywords:Phospholamban, Heart failure, Ion-affinity modulators, SPCA, SERCA, P-type ion transporters, Na+K+ATPase

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences