FP6 priority
1.1.1   Genomics and Biotechnology for Health
1.1.2.1
Title of the proposal

The role of plasmalemmal ATPases in maintenance of the intracellular homeostasis of ions and termination of purinergic signal

Institute
Slovak Academy of Sciences, Institute for Heart Research
Dubravska cesta 9, 84233 Bratislava, Slovak Republic
www.usrd.sav.sk
Contact
Name:
Norbert VRBJAR, PhD.
Phone:
+421 2 54776637
E-mail:
usrdnorb@savba.sk


Research subject for a potential FP6 project

On the cellular level the first site where the cells respond to various extracellular impulses is the plasmalemmal membrane. Among the most important impulses modifying the enzymatic and transport functions of integrated plasmalemmal proteins belong the impulses which influence the transmembraneous iontransport and the regulation of intracellular processes via purinoceptors. In plasmalemmal membranes of almost all tissues two types of ATPases are present. One of them hydrolyses extracellular ATP and on this way is involved in termination of action of extracellular ATP which acts on P2-purinoceptos. It has been proposed that the initial vasodilation of the vasculature in response to hypoxia or ischemia is due largely to the release of ATP. Substantial evidence has accumulated to suggest that ATP is released from vascular endothelial cells (including those in coronary vessels) during hypoxia and ischemia. In plasmalemmal membranes the ectoATPase is activated to a similar extent by either Ca2+ or Mg2+ and id has a broad nucleotide-hydrolysing activity, i.e. it can hydrolyse ATP, GTP, UTP, CTP, ADP, GDP to a similar extent. The second type of ATPases in pasmalemmal membranes like the Na,K-ATPase hydrolyses the intracellular ATP and utilizes the derived energy for iontransport processes against the concentration gradient of K+ and Na+ ions.

The present project proposal is oriented to the role of plasmalemmal Ca-dependent ectoATPase, Mg-dependent ectoATPase as well as the Na,K-ATPase in various physiological and pathophysiological situations. Study of kinetic parameters for the above enzymes will be used as a tool to estimate the properties of the substrate and cofactor binding sites in cardiac and renal tissues of rats with experimentally induced ischemia, hypertension and diabetes.


Recent international cooperation of the research team



Proposerīs relevant publications related to the research subject

1. Vrbjar, N., Dzurba, A., Ziegelhoffer, A. (1993): Kinetic and thermodynamic properties of membrane bound Ca-ATPase with low affinity to calcium in cardiac sarcolemma; response to global ischemia of the heart. Life Sci., 53, (24), 1789-1794.
2. Vrbjar, N., Dzurba, A., Ziegelhoffer, A. (1995): Influence of global ischemia on the sarcolemmal ATPases in the rat heart. Mol. Cell. Biochem. 147, (1/2), 99-103. 3. Vrbjar N., Bernatova I., Pechanova O. (1999): Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension. Mol. Cell. Biochem. 202, 141-147.
4. Vrbjar N., Strniskova M., Pechanova O., Gerova M. (2000): Short-term NO synthase inhibition and the Na+-binding properties of cardiac Na,K-ATPase. Physiol. Res. 49, 65-70.