Calcium Channels: Introduction into Their Molecular Pharmacology

Abstract

Calcium has a central role in cellular physiology. It mediates contraction of cardiac, smooth and skeletal muscle, neurotransmitter and hormone release, egg fertilization, acts as an intracellular signal regulating key enzymes in metabolism, controls cell differentiation and growth and plays a role in the immune response. Voltage- or receptor operated calcium specific channels in plasmamembranes are important regulators of calcium entry into cells. Despite sophisticated electrophysiological methods, the structural features and the molecular pharmacology of the calcium channel remained completely unexplored until 1981. In this year our group reported that the radiolabelled 1,4-dihydropyridine ³H-nitrendipine binds to stereoselective drug receptor sites in cardiac membranes [1]. Since that time rapid progress has been made with respect to the biochemical characterisation of the calcium channel. These findings have advanced our understanding of the action of drugs which alter the channel function and have led to new concepts and hypotheses. The german physiologist Fleckenstein [2] not only paved the way for a new useful pharmacodynamic concept (with important therapeutic consequences) but also discovered and classified the tools which were essential to extend calcium channel research to the molecular level. As the calcium antagonist binding sites are evolutionary preserved and occur in plants, electric eel membranes, non electrically excitable tissues (as are human red blood cells), calcium channel drug research will grow in the next few years and extend from agriculture to neurochemistry.