Function and regulation of calcium channels in the cardiovascular system

• Applicant: Privatdozent Dr. Sven Moosmang
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 49558454

Ion channels are responsible for the movement of ions across cell membranes and, therefore, an essential prerequisite for many of life´s processes like muscle contraction or gene transcription. Voltage-gated L-type Ca2+ channels are essential for the control of the intracellular Ca2+ concentration in excitable and non-excitable cells. The influx of Ca2+ through the CaV1.2 L-type channel is essential for activation of excitation-contraction coupling in the cardic muscle and sinus node. The aim of this project is to resolve the regulation and biological function of Ca2+ channels in the cardiovascular system. The priority objective of this grant proposal consits of the generation and analysis of mouse lines with (1) a PKA-insensitive CaV1.2 using a knock-in approach with targeted mutation of S1928 of the channel to alanine, (2) a sinus node specific, inducible knock-out of CaV1.2 using HCN4-Cre mice (in the close collaboration with Prof. Ludwig, Erlangen), (3) a CaV1.2 lacking calcium dependent inactivation using knock-in approach with targeted mutation of I1624 of the channel to glutamate and (4) a CaMKII-insensitive CaV1.2 using a knock-in approach with targeted mutation of serines 1512 and 1570 of the channel to alanine.

• DFG Programme: Research Grants
• Participating Person: Privatdozentin Dr. Andrea Welling