VEGA 2/0195/10

Regulation of the gating of the T-type calcium channel        


Principal Investigator: Ľubica Lacinová

Duration: January 2010 – December 2012
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava


Enhanced activity of low-voltage-activated (LVA) calcium channels is involved in pathology of several neurological diseases including childhood absence epilepsy. These channels are distinguished from high-voltage-activated calcium channels by low activation threshold, fast kinetics of activation and inactivation and slow deactivation. We will concentrate on identification of structural determinants of specific gating properties of the CaV3.1 channel, representative of LVA channels. For this aim we will construct series of channel mutants targeting putative interaction site between the channel voltage sensor and the channel conductive pore. Further, we will analyse role of regions in which single nucleotide polymorphism for childhood absence epilepsy were reported. Based on our results functional model of the CaV3.1 channel gating will be developed.


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image Karmazinova M., Lacinova L. (2010): Removal of the outermost arginine in IVS4 segment of the Cav3.1 channel affects amplitude but not voltage dependence of gating current. Gen Physiol Biophys 29:419-423.
image Karmazinová M, Beyl S, Stary-Weinzinger A, Suwattanasophon C, Klugbauer N, Hering S, Lacinová L (2010): Cysteines in the loop between IS5 and the pore helix of Ca(V)3.1 are essential for channel gating. Pflugers Arch 460:1015-1028.
image Karmazinova M., Lacinova L. (2010): Measurement of cellular excitability by whole cell patch clamp technique. Physiol Res 59:1-7.
image Lacinová Ľ. (2011): T-type calcium channel blockers-new and notable. Gen Physiol Biophys 30:403-409.
image Karmažínová M, Baumgart JP, Perez-Reyes E, Lacinová L (2011): The voltage dependence of gating currents of the neuronal Ca(v)3.3 channel is determined by the gating brake in the I-II loop. Pflugers Arch 461:461-468.
Weiss N, Hameed S, Fernández-Fernández JM, Fablet K, Karmazinova M, Poillot C, Proft J, Chen L, Bidaud I, Monteil A, Huc-Brandt S, Lacinova L, Lory P, Zamponi GW, De Waard M (2012): A Ca(v)3.2/syntaxin-1A signaling complex controls T-type channel activity and low-threshold exocytosis. J Biol Chem 287:2810-2818.