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

Modulation of single channel properties of mitochondrial K-ATP and permeability transition pore channels.

Institute
Slovak Academy of Sciences, Institute of Molecular Physiology and Genetics
Vlarska 5, 83334 Bratislava, SLOVAK REPUBLIC
www.umfg.sav.sk
Contact
Name:
Karol ONDRIAS, PhD, DSc.
Phone:
+421 2 54774102
E-mail:
umfgonds@kramare.savba.sk


Research subject for a potential FP6 project

Mitochondria play an important role in cardioprotection. However molecular mechanism of the protection is not fully understood. It is supposed that K-ATP and permeability transition pore (PTP) mitochondrial channels might be responsible for the cardioprotection. However, their electrical single channel properties are mostly unknown.
Therefore aim of the present project is to study single channel properties and endogenous and exogenous modulation of the channels. We plan to identify the gene structure and to evaluate the gene expression of these channels. We will isolate mitochondrial membranes from rat heart and incorporate them into bilayer lipid membrane (BLM). Using the method of voltage clamp we plan to study modulation of their single channel properties. Particularly influence of: pH, ATP, Ca2+ and NAADP and exogenous modulation (influence of: diazoxide, 5-HD and cyklosporin) on electrical properties of single K-ATP channel permeable for potassium and on PTP channel permeable for calcium.
Results will contribute to understand function of mitochondria in normal and pathological conditions and explain their cardioprotective function at molecular level. This knowledge may contribute to prevent and cure cardiovascular diseases.


Recent international cooperation of the research team

Adam Szewczyk, PhD, DSc
Nencki Institute of Experimental Biology
Polish Academy of Sciences
Pasteura 3, 02-093 Warsaw, POLAND


Proposerīs relevant publications related to the research subject

1. KOMINKOVA V, RAVINGEROVA T, MALEKOVA L, ONDRIAS K: SINGLE CHANNEL PROPERTIES OF POTASSIUM CHANNELS FROM HEART MITOCHONDRIA. 78TH PHYSIOLOGICAL DAYS. PROGRAM AND ABSTRACTS P. 45, PIESTANY 2002, SLOVAKIA
2.Kominkova, V., Ondrias, K. KATP channels in rat heart mitochondrial membranes. Poster on the 4th czech-french-slovak symposium: New frontiers in basic cardiovascular research, Marianske Lazne 2000, Czech Republic
3.Kominkova, V., Malekova L., Ondrias K.: Potassium channels in rat heart mitochondrial membranes. Program IBRO Summer School 2001, Tihany, Hungary, p. 27