Understanding the molecular processes by which ionic channels are regulated is central to the understanding of cellular function. Great advances in understanding these regulatory mechanisms have been recently achieved by the combination of several powerful techniques. Development of the patch clamp technique, ability to access the intracellular channels sites, and genetic manipulation of channel structure have allowed studies of channel function in native membranes. Cloning, sequencing and determining the channel structure and its subunits allows further insight into the regulatory mechanisms of channel function. In planning this symposium, we organized the scientific discussions around specific molecular topics independent of the tissue and species of origin. Clearly, the subject of ion channel regulation is multi-faceted, with a large number of very talented scientists working in the field. The NATO Symposium represented an attempt to bring together these individuals and synthesize and evaluate new ideas and experimental findings. A great deal of novel data was presented, and scientific insight into the molecular processes which regulate ionic channels was furthered. This book gives a synopsis of the scientific presentations and is organized into 3 sections. The first section deals with the diversity of K + channels and their regulation, including structure-function and mechanistic studies. Presentations dealt with the characterization and modulation of a variety ofK+ channels in cardiac and neuronal cells, including ATP­ dependent K+ channels, Na + -activated K+ channels, delayed rectifier K+ channels and the diversity of their regulation by G-proteins.

Inhalt

I: Regulation of K+ Channels.- K+ channel diversity.- Regulation of voltage-activated K+ channels.- Gating mechanisms of Shaker potassium channels.- Vaccinia virus: A novel expression system for receptors and ion channels.- Delayed rectification in the heart: Regulation and physiology.- Receptor-dependent modulation of G protein-gated muscarinic K+ channel by arachidonic acid metabolites.- The Na+-activated K+ channel in cardiac cells.- Regulation of the ATP-dependent K+ channel of muscle by ATP and pH.- Regulation of cardiac ATP-sensitive K+ channels.- ATP-sensitive K+ channels: Molecular pharmacology, regulation and role in diseased states.- II: Regulation of Ca2+ Channels.- Tissue distribution and possible function of the subunits of the L-typ calcium channels.- Phosphorylation and regulation of calcium channels by multiple protein kinases.- Action of the GTP-binding protein Gs on cardiac Ca2+ channels.- Membrane-delimited stimulation of heart cell calcium current by ß-adrenergic signal-transducing Gs protein.- Participation of a fast G-protein pathway in the ß-adrenergic regulation of cardiac calcium channels: Neither proven nor needed.- Kinetics of G-protein mediated action on neuronal Ca2+ channels.- Identification of G-proteins involved in the inhibition of Ca2+ currents in neuronal and endocrine cells.- Voltage-dependent ?-adrenergic modulation of Ca2+ channels in peripheral neurons and insulin-secreting cells.- Voltage-dependent modal gating in cardiac and neuronal L-type calcium channels.- T-type calcium channels in cardiac muscle: News in kinetics and modulation.- Calcium regulation of ion channels in neurons.- Role of calpastatin in calcium channel regulation.- III: Regulation of Na+, Cl?, and If Channels.- Structure and modulation of voltage-gated sodium channels.- Regulation of the cAMP-dependent chloride current in cardiac ventricular myocytes.- Magnesium as an intracellular modulator of calcium, potassium and chloride channels.- Cyclic AMP regulation of pacemaker (If) current in heart.