APVV-0212-10

Calcium channels in neuronal excitability

Principal Investigator: Ľubica Lacinová
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava, Slovak Republic

Duration: May 2011 – October 2014

Annotation:

Voltage-gated Ca2+ channels (VGCCs) mediate influx of Ca2+ ion, which controls a number of processes including neuronal development and plasticity. L-type voltage-gated Ca2+ channels represent a well-established therapeutic target. Known L-VGCC isoforms (Ca_v1.2, Ca_v1.3 and Ca_v1.4) possess different biophysical properties, thus differentially affecting the dynamics of Ca2+ influx and electrical excitability. This raises a question, to which extent these isoforms contribute to various cellular functions. We will use two established models of neurogenesis: PC12 cell line and primary culture of hippocampal neurons. To analyze role of specific subtypes of L-VGCC we will use method of gene silencing. First we shall optimize cell transfection by siRNA and analyze alteration of structure and function of cell membrane. To assess contribution of Ca_v1.2 and/or Ca_v1.3 channels to cellular excitability we will employ whole cell patch clamp measurements. Activity of L-VGCC is in direct relation with activity of other surface transport proteins like Na-Ca-exchanger or Na-K-ATPaze and with activity of intracellular calcium channels like IP3 receptors. We will analyze possible alterations in their expression by PCR method. Altered ratio of transport proteins may affect cell architecture. We will use electron microscopy to assess changes in cell ultrastructure.

Publications:

• Lacinová L (2011): T-type calcium channel blockers – new and notable. Gen Physiol Biophys 30:403-409.
• Caro A, Tarabova B , Rojo-Ruiz J, Lacinova L (2011): Nimodipine inhibits action potential firing in cultured hippocampal neurons predominantly due to block of voltage-dependent potassium channels. Gen Physiol Biophys 30: Sp. Issue 1. S44–S53.
• Lacinova L (2004):Pharmacology of recombinant low-voltage activated calcium channels. Current Drug Targets – CNS & Neurological Disorders 3:75-81.
• Uhríková D, Kučerka N, Lengyel A, Pullmannová P, Teixeira J, Murugova T, Funari SS, Balgavý P (2012): Lipid bilayer – DNA interaction mediated by divalent metal cations: SANS and SAXD study. SANS YuMO user meeting, May 27 – 30, 2011, Dubna. J. Phys. – Conference Series 351:1-9 (012011).
• Mallmann RT, Wilmes T, Lichvarova L , Bührer A, Lohmüller B, Castonguay J, Lacinova L, Klugbauer N (2013): Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels. Sci Rep 3:1777.
• Jaskova K, Pavlovicova M, Cagalinec M, Lacinova L, Jurkovicova D (2014): TGFβ1 downregulates neurite outgrowth, expression of Ca2+ transporters, and mitochondrial dynamics of in vitro cerebellar granule cells. Neuroreport 25:340-346.
• Hubčík L, Pullmannová P, Funari SS, Devínsky F, Uhríková D (2014): DNA-DOPC-Gemini surfactants complexes: effect of ionic strength. Acta Fac Pharm Univ Comen 61:26-34.
• Belička M, Kučerka N, Uhríková D, Islamov AKh, Kuklin AI, Devínsky F, Balgavý P (2014): Effect of N,N-dimethyl-N-alkylamine-N-oxides on DOPC bilayer in unilamellar vesicles: small-angle neutron scattering study. Eur Biophys J 43:179-189.
• Karmažínová M, Jašková K, Griač P, Perez-Reyes E, Lacinová Ľ (2015): Contrasting the roles of the I-II loop gating brake in CaV3.1 and CaV3.3 calcium channels. Pflugers Arch 467:2519-2527.
• Pavlovicova M, Lacinova L, Dremencov E (2015): Cellular and molecular mechanisms underlying the treatment of depression: focusing on hippocampal G-protein-coupled receptors and voltage-dependent calcium channels.Gen Physiol Biophys 34:353-366.
• Lichvárová L, Lacinová Ľ (2015): Ca(V)1.2 and Ca(V)1.3 L-type calcium channels regulate the resting membrane potential but not the expression of calcium transporters in differentiated PC12 cells. Gen Physiol Biophys 34:157-65.
• Hubčík L, Funari SS, Pullmannová P, Devínsky F, Uhríková D (2015): Stimuli responsive polymorphism of C12NO/DOPE/DNA complexes: effect of pH, temperature and composition. Biochim. Biophys. Acta – Biomembranes 1848:1127-1138.
• Uhríková D (2015): Lipoplexy – nevírusové prenosové vektory na báze fosfolipidov. , v Uhríková a kol.: Biofyzika – Vybrané kapitoly, UK, Bratislava, 2015, vysokoškolská učebnica – el. zdroj, str. 136 -160.
• Ondáčová K, Jurkovičová D, Lacinová Ľ (2016): Altered sodium and potassium, but not calcium currents in cerebellar granule cells in an in vitro model of neuronal injury. Cell Mol Neurobiol 37: 771–782.