Transmembrane Calcium channels are found in all excitable and many non-exictable cells. They carry out an important dual role: (1) The depolarizing current generated by the time- and voltage dependent openings of Ca channels determines impulse initiation, rhythmic activity, impulse conduction and refractoriness in many cells. (2) Perhaps even more importantly, entering Ca ions also carry a specific message to be decoded by cellular Ca receptor proteins. In linking membrane depolarization to the delivery of a messenger substance, Ca channels perform a function that is vital and possibly unique. The Ca signal leads to the initiation of contraction in heart and smooth muscle, transmitter release from nerve terminals and exocytotic secretion by gland cells. Not surprisingly, Ca channel activity is tightly regulated. The list of known control systems acting on Ca channels is growing steadily and involves endogenous substances such as hormones, neurotransmitters and intracellular mediators as well as several classes of organic drugs with great therapeutic value. The purpose of this conference sponsored by the New York Academy of Sciences is to highlight the remarkable progress achieved over the last few years. Advances were mainly possible because of the development of new Ca channel ligands and of new methods for the detailed functional investigation of single Ca channel molecules. Thus several distinct Ca channel types with different biophysical, physiological, pharmacological and regulatory properties have been identified. New models for the mechanisms of ion permeation and channel gating have been developed. New high-affinity ligands have allowed the chemical purification and elucidation of the subunit composition of at least one channel type, the localization of channel distribution as well as the observation of Ca channel expression during development and in various diseases. Finally, new clinical correlations are becoming apparent: Antibodies against Ca channels have been implicated in the pathogenesis of Lambert-Eaton Myasthenic Syndrome and a specific lack of Ca channels has been demonstrated in muscular dysgenesis. The study of Ca channels has thus evolved into a truly multi- disciplinary effort. The conference will bring together scientists from neurobiology, biochemistry, molecular biology, physiology and pharmacology, each contributing a vital part to the understanding of this highly relevant biological signalling pathway.
