Stimulus-secretion coupling: a perspective highlighting the contributions of Peter Baker.

Many investigators are using numerous preparations for contributing to our present understanding of stimulus-secretion coupling, by which we mean stimulus-dependent exocytosis, sometimes known as the regulated pathway. However, a few model systems have been particularly illuminating and several of these were exploited by Peter Baker and his close associates: namely, the motor nerve terminal, the adrenal chromaffin cell, the sea urchin egg and the blood platelet. In fact, Peter's first real contribution in this area came from his seminal studies on calcium transport in his favourite preparation, the squid giant axon, where he investigated Ca2+/Na+ exchange, Ca2+ distribution and voltage-gated Ca2+ entry. More direct investigations into stimulus-secretion coupling came from work on neurone transmitter release in collaboration with Andrew Crawford, and on catecholamine secretion from the adrenal medulla in collaboration (with TJR). His most important generic contribution to this field was in the development (with DEK), of the electropermeabilized cell, which allows control of the low molecular weight components of the cytosol while leaving the exocytotic apparatus and process intact. In the initial experiments on the cells it was finally proved that Ca2+-dependent secretion of catecholamines is indeed from the granules and not from the cytosol. The quantification of the Ca2+ requirement of secretory exocytosis was an important step, as was the investigation of many factors purported to be important in the coupling mechanism or in the exocytotic process itself. Work with the human platelet, using this technique, has proved to be especially valuable in unravelling the complex interactions between different second messengers and has been neatly complemented by work in intact cells containing Ca2+-indicator fluorescent dyes. Peter was also intrigued by post-secretory events both in the early seventies, and at the end of his career when he embarked on analysis of the membrane retrieval process and the associated uptake of extracellular medium.