MRTN-CT-2006-035367

CavNet L-type calcium channels in health and disease        

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Coordinator: Hearing Reasearch Centre Tübingen, Eberhard Karls University, Tübingen, Germany
Principal investigator at IMPG SAS: Ľubica Lacinová

Duration: December 2006 – Deecember 2010
Coordinating Organization: Hearing Reasearch Centre Tübingen, Eberhard Karls University, Tübingen, Germany

Annotation:

Ca2+ channels have a unique role in cellular signaling, mediating plasmalemmal Ca2+ ion influx. This results in elevated intracellular free Ca2+ concentration which, in turn, controls a number of important biological processes, like secretion in neurons and endocrine cells and muscle contraction. Voltage-gated Ca2+ channels (VGCCs) are found in all electrically excitable cells. They consist of a pore-forming ?1 subunit and several accessory subunits. Among this ion channel family, L-type voltage-gated Ca2+ channels (L-VGCCs) represent a well-established therapeutic target for so-called Ca2+ antagonists (Ca2+ channel blockers), which are widely used to treat hypertension and myocardial ischemia. Recently L-VGCCs outside the cardiovascular system have received special attention because they control key physiological processes such as neuronal plasticity, sensory cell function (e.g. in inner ear and retina), and endocrine function (e.g. pancreatic islets, adrenal medulla). L-VGCC research was particularly stimulated by the discovery that the known L-VGCC isoforms expressed in these tissues (Cav1.2, Cav1.3 and Cav1.4) possess different biophysical properties, thus differentially affecting the dynamics of Ca2+ influx and electrical excitability. This raises two important questions: 1) to which extent do these isoforms contribute to various cellular functions? 2) once this is known, would it be possible to develop selective Ca2+ channel modulators to treat human diseases?

Defended works during project: 

Anton Caro successfully defended PhD thesis: ”Voltage dependent calcium channels in rodent hippocampus” in March 2012

Publications:

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image Tarabova B, Lacinova L, Engel J (2007): Effects of phenylalkylamines and benzothiazepines on Cav3 − mediated Ca2+ currents in neonatal mouse inner hair cells. Eur J Pharmacol 573:39-48.
image Vandael D H, Marcantoni A, Mahapatra S, Caro A, Ruth P, Zuccotti A, Knipper M and Carbone E (2010): Ca(v)1.3 and BK channels for timing and regulating cell firing. Mol Neurobiol 42:185-198.
image 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.
image Jurkovičová-Tarabová B, Griesemer D, Pirone A, Sinnegger-Brauns M J, Striessnig J and Friauf E (2012): Repertoire of high voltage-activated Ca2+ channels in the lateral superior olive: functional analysis in wild-type, Ca(v)1.3(-/-), and Ca(v)1.2DHP(-/-) mice. J Neurophysiol 108:365-79.