Preamble

Ion channels are a prerequisite for normal cellular function of all organs.
For this reason, a better understanding of their function constitutes an essential basis for understanding widespread human diseases causing a high social and economic burden. Disturbances in ion channel function lead to serious diseases of the nervous system, skeletal and cardiac muscle, and intestine which makes ion channels important drug targets for the pharmaceutical industry.

Calcium currents through L-type voltage-gated Ca2+ channels (L-VGCCs) play a key role in the cellular signalling in brain, heart, smooth muscles, sensory (e.g. inner ear, retina), and endocrine cells (e.g. pancreatic islets). In distinct cells of these organs, the pore forming 1-subunits Cav1.2 and/or Cav1.3 conduct Ca2+ currents that are required for their function.

To address the important question about the differential contribution and functional communication of these L-VGCC isoforms and their potential role in other tissues an already existing network of collaborating scientists will be complemented by excellent researchers providing the required advanced research methods and front-end ion channel expertise. As Cav1.2 and Cav1.3 show an overlapping expression pattern in a variety of tissues and subunit-specific antagonists or agonists are not available so far, genetic tools are urgently needed to dissect the specific roles of both Cav1.2 and Cav1.3 in normal and pathological function. This consortium will complement its existing mouse models by new ones and will apply state of the art molecular biological, electrophysiological, Ca2+ imaging techniques and behavioural analyses to reveal the physiological role and pharmacotherapeutic potential of these channels with a special focus on brain function (anxiety and depression, age-induced changes in cognitive function, learning and memory; Alzheimer disease, posttraumatic stress syndrome, epilepsy), cardiac function (sino-atrial node and conduction system, genesis of arrhythmias and regulation of the blood pressure), pancreatic endocrine function (somatostatin, insulin and glucagon release, diabetes mellitus), sensory function (hearing, tinnitus, deafness) and neuronal development.

The long standing and complementary expertise of the network partners will not only advance our understanding of the role of individual L-VGCC subtypes in health and disease but also provide a stimulating and highly productive research training platform for young researchers in modern cell biological, molecular, physiological and pharmacological techniques. The proposed research on L-VGCCs in different organs not only represents an important scientific task but also provides an excellent opportunity for an integrative and interdisciplinary but appropriately focussed training in the field of signal transduction in general and ion channels in particular.