The SAS proposals for participation in FP6 projects
are listed in blocks according to the FP6 priority theme structure

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

Properties and regulation of T-type calcium channel.

Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences
Vlarska 5, 833 34 Bratislava, Slovak Republic
Lubica Lacinova, RNDr. PhD.
+421 2 54773800 ext.320

Research subject for a potential FP6 project

Contribution of T-type calcium channels to the cell excitability is investigated. Initial phase of action potential is co-regulated by activation of low-voltage activated (LVA) calcium channels. Therefore regulation of LVA channels may affect e.g. frequency of generation of action potentials. Possibility of specific pharmacological regulation of T-type calcium channel would open whole new field in treatment of various diseases. Recent cloning of three representatives of low-voltage activated channel family 1G (Cav3.1 according to new nomenclature), 1H (Cav3.2) and 1I (Cav3.3) enabled studies of their electrophysiological characteristics, pharmacology, and subunits composition. T-type calcium current is measured in HEK 293 cell line transfected with Cav3.1 channel using whole cell patch clamp method. Various permeant ions and various voltage protocols will be used to characterize basic biophysical properties of the channel. Experimental data will be analyzed using Boltzmann, Goldmann-Hodgkin-Katz and Hodgkin-Huxley theories. A model enabling involvement of T-type calcium channel into model of cardiac action potential will be outlined. Regulation of the channel kinetics by physiological or pathophysiological stimuli, e.g., phosphorylation, change in pH or NO-dependent pathway will be investigated.

Recent international cooperation of the research team

Institute for Pharmacology and Toxicology Technical University Munchen, Munchen, Germany

Proposer´s relevant publications related to the research subject

1. Klugbauer N., Marais E., Lacinova L., Hofmann F. (1999): A T-type calcium channel from mouse brain. Pflugers Arch., 437: 710 - 715.
2. Lacinova L., Klugbauer N., Hofmann F. (1999) Absence of modulation of the expressed calcium channel 1G subunit by 2 subunits. J. Physiol., 516: 639 - 645.
3. Lacinova L., Klugbauer N., Hofmann F. (2000) Regulation of the calcium channel 1G subunit by divalent cations and organic blockers. Neuropharmacology, 39: 1254 - 1266.
4. Lacinova L., Klugbauer N., Hofmann F. (2000) Low voltage activated calcium channels: from genes to function. Gen. Physiol. Biophys., 19: 121 – 136.
5. Staes M., Talavera K., Klugbauer N., Prenen J., Lacinova L., Droogmans G., Hofmann F., Nilius B. (2001) The amino side of the C-terminus determines fast inactivation of the T-type calcium channel a1G J. Physiol. (London), 530: 35 – 45.