nd The 22 meeting of the International Society on Oxygen Transport to Tissue (LS. O. T. T. ) of which this volume is the scientific proceedings, was held in Istanbul, Turkey on August 22-26, 1994. It was a historical occasion in that it was almost 200 years to the day that one of the founding fathers of oxygen research, Antoine Lavoisier, on May 8, 1794 found his early demise at the hands of the guillotine. This spirit of history set the tone of the conference and in the opening lecture the contribution that this part of the world has given to the understanding of oxygen transport to tissue was highlighted. In particular, the contribution of Galen of Pergamon (129-200) was discussed who for the first time demon strated that blood flowed through the arteries and whose view on the physiology of the circulation dominated the ancient world for well over a millennium. A forgotten chapter in the history of the circulation of the blood is the contribution made by Ibn al Nafis of Damascus (1210-1280) who for the first time described the importance of the pulmonary circulation by stating that all venous blood entering the right ventricle ofthe heart passes to the left ventricle, not through pores in the septum of the heart as had been postulated by Galen, but through the circulation of the lungs."

There are more than 6000 species belonging to twenty-seven orders in the Class Mammalia. Comparative studies of this diverse and magnificent array of extant species provide valuable opportunities to formulate and test hypotheses concerning the evolution of reproduction. This is the first book to explore, in depth and breadth, the complex interrelationships that exist between patterns of mating behaviour and the evolution of mammalian reproductive anatomy and physiology. It focuses upon the role that copulatory and post-copulatory sexual selection have played during the evolution of the monotremes, marsupials and placental mammals, and examines the effects of sperm competition and cryptic female choice upon coevolution of the genitalia in the two sexes. In addition, due weight is also given to discussions of the modes of life of mammals, and to the roles played by natural selection and phylogeny in determining their reproductive traits.

B. Raymond Fink Sheldon Roth and Keith Miller have asked me to record that the Third Conference on Molecular and Cellular Mechanisms of Anesthesia was held in Calgary last May "in my honor. " Such was my dear friends' gracious way of continuing a series that began at the University of Washington, where I hosted two, four, or five previous ones, 1,3-6 depending 2 on how far back one wishes to count. At that, Seattle took up where Paris left off in 1951. These occasions create their own unforgettable memories. This book captures the fine, invigorating ambience of the University of Calgary and the exciting explorations and com panionship of a gathering in a frontier territory of neuroscience. So, floreant symposia. They have progressively refined the quarry, from pathway to synapse to lipoprotein membrane to receptor and single channel, in heuristic convergences of neuronal physiology, biochemistry, and pharmacology. Nevertheless, the anesthesiologist in me senses a certain disquiet, a certain claustrophobia provoked by the narrow confines of micropipettes. How much more tubular must tunnel vision become before the desired broad view emerges? At present, the advances in molecular neurobiology seem continually to increase the apparent complexity of the total problem and the conceptual distance between the reductionists in the laboratories and the holists in the operating rooms. Happily, what is also growing is the excitement in trying to bridge the gap. Perhaps it would be timely to regard general anesthesia not as a state but as a syndrome."

The Springer Handbook oj Auditory Research presents a series of com prehensive and synthetic reviews of the fundamental topics in modern auditory research. It is aimed at all individuals with interests in hearing research including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes will introduce new investigators to important aspects of hearing science and will help established investigators to better understand the fundamental theories and data in fields of hearing that they may not normally follow closely. Each volume is intended to present a particular topic comprehensively, and each chapter will serve as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in peer-reviewed journals. The series focuses on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beginning to develop. New research areas will be covered on a timely basis in the series as they begin to mature. Each volume in the series consists of five to eight substantial chapters on a particular topic. In some cases, the topics will be ones of traditional interest for which there is a solid body of data and theory, such as auditory neuroanatomy (Vol. 1) and neurophysiology (Vol. 2). Other volumes in the series will deal with topics which have begun to mature more recently, such as development, plasticity, and computational models of neural processing."

This volume contains the papers presented at the International Symposium on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," held in Valencia, Spain, De- cember 2nd_4th, 1996. Liver cirrhosis is one of the main causes of death in occidental countries. There are other hepatic dysfunctions such as fulminant hepatic failure, Reye's syndrome, or congenital deficiencies of urea cycle enzymes which can also lead to hepatic encephalopathy, coma and death. However, the molecular bases ofthe pathogenesis of hepatic encephalopathy remain unclear. One ofthe consequences of hepatic failure is the reduced ability to detoxify ammonia by incorporating it into urea. This leads to increased blood ammonia levels. Hyperam- monemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy and classical clinical treatments are directed towards reducing blood ammo- nia levels. Altered neurotransmission is an essential step in the pathogenesis of hepatic encephalopathy. The first part of the book is devoted to the discussion of the recent advances in the understanding of the alterations of different neurotransmitter systems in hepatic encephalopathy. The alterations of tryptophan metabolism and neurotransmission in hepatic encephalopathy and the implications for the clinical use of neuropsychoactive drugs are reviewed. The alterations in glutamate transport and neurotransmission in hepatic encephal- opathy due to acute liver failure are also reviewed. The role of NMDA receptors in the molecular mechanism of acute ammonia toxicity is discussed as well as its modulation by metabotropic glutamate receptors and muscarinic receptors.

The Third International Symposium on Excitation-Contraction Coupling in Skeletal, Cardiac, and Smooth Muscle, organized by George Frank, C. Paul Bianchi, and Henk E. DJ. ter Keurs, was held in Banff Centre, Banff, Alberta, Canada during June 26 to June 30, 1991. The theme of these symposia has been to recognize the similarities and dissimilarities of excitation-contraction coupling in skeletal, cardiac, and smooth muscle. Cross fertilization of concepts of excitation-contraction coupling in these three types of muscle has occurred since the early studies in the late fifties and early sixties on skeletal muscle. Investigators in each field meet only at specialized symposia which exclude investigators in the other fields. The purpose of the symposia has been to bring together international investigators studying excitation-contraction coupling in skeletal, cardiac, and smooth muscle so that we may learn from each other and hence provide a more global concept of excitation-contraction. The Third International Symposia has accomplished its objective as we recognize that calcium channels of the sarcolemma and the sarcoplasmic reticulum play key essential roles in excitation-contraction coupling in all three types of muscles. In skeletal muscle the recognition that E-C coupling consists of two parallel mechanisms, one dependent upon a dihydropyridine voltage-sensitive sensors coupled to calcium release from the terminal cisternae via the ryanodine sensitive channel in the foot structure of the triad.

`Are the Great Lakes getting better or worse?' This is the question that the public, scientists and managers are asking the International Joint Commission after a quarter-century of cooperative action by the United States and Canadian governments to clean up the Great Lakes. This volume contains papers from the workshop on Environmental Results, hosted in Windsor, Ontario, by the Great Lakes Science Advisory Board of the International Joint Commission, on September 12 and 13, 1996. The Great Lakes have been through almost a century of severe pollution from the manufacture, use and disposal of chemicals. In the 1960s wildlife biologists started to investigate the outbreaks of reproductive failure in fish-eating birds and ranch mink and to link these to exposure to organochlorine compounds. Human health researchers in the 1980s and 1990s linked growth retardation, behavioral anomalies and deficits in cognitive development with maternal consumption of Great Lakes fish prior to pregnancy. The Great Lakes became the laboratory where the theory of endocrine disruptors was first formulated. Now a group of Great Lakes scientists, hosted by the International Joint Commission, has compiled the story of the trends in the concentrations and effects of persistent toxic substances on wildlife and humans. The technical papers review the suitability of various organisms as indicators, and present the results of long-term monitoring of the concentrations and of the incidence of effects. The evidence shows that there was an enormous improvement in the late 1970s, but that in the late 1990s there are still concentrations of some persistent toxic substances that have stubbornly remained at levels that continue to cause toxicological effects.

Wide and fascinating is the field of research on tryptophan, a most versatile amino acid, transformed, as it is, in our organism into many biologically active substances. This volume contains the proceedings of the Eighth International Meeting on Tryptophan Research, held at the University of Padova, Padova, Italy, from June 25 to 29 1995, under the auspices of the University of Padova, National Research Council, Italian Chemical Society-Division of Pharmaceutical Sciences, Region ofthe Veneto and City of Padova. The meeting was held in Padova to commemorate Prof. Luigi Musajo twenty years after his death and the editors dedicate this book to him in recognition of his pioneering work in tryptophan metabolism. Prof. Osamu Hayaishi delivered the Musajo Memorial Award Lecture: Tryptophan oxygenase. and sleep. Figure I shows the ISTRY President Prof. Simon N. Young presenting the Musajo Memorial Medal to Prof. Hayaishi during the Opening Ceremony. Two hundred scientists from twenty two countries participated in the meeting. These proceedings contain 121 papers encompassing a variety of topics and disciplines.

A wealth of information has been accumulated about the function of ion channels of excitable cells since the extensive and pioneering voltage clamp studies by Hodgkin, Huxley, and Katz 36 years ago. The study of ion chan nels has now reached a stage at which a quantum jump in progress is antici pated. There are many good reasons for this. Patch clamp techniques origi nally developed by Neher and Sakmann 12 years ago have made it possible to study the function of ion channels in a variety of cells. Membrane ionic currents can now be recorded practically from many types of cells using the whole-cell patch clamp technique. The opening and closing of individual ion channels can be analyzed using the single-channel patch clamp method. Techniques have also been developed to incorporate purified ion channels into lipid bilayers to reconstitute an "excitable membrane. " Advanced tech niques developed in molecular biology, genetics, and immunology, such as gene cloning and the use of monoclonal antibodies, are now being applied to the study of ion channels. A variety of drugs have now been found or are suspected to interact with ion channels to exert therapeutic effects. In addition to the classical exam ples, as represented by local anesthetics, many other drugs, including cal cium antagonists, psychoactive drugs, cardiac drugs, and anticonvulsants, shown to alter ion channel function. For certain pesticides such as have been pyrethroids and DDT, sodium channels are clearly the major target site.

This book has a dual purpose, to review in depth the control of fuel homeostasis in the brain and the role of the nervous system in the control of fuel deposition in the body. From the methodological point of view the emphasis is on the application of advanced technologies to assess fuel transport and brain metabolism, the role of peptides in the neuroendocrine system and the response of the brain to hypoglycemia. These technologies include positron emmission tomography, nuclear magnetic resonance, immunocytochemistry, molecular biology, autoradiography. To study fuel homeostasis in the body advanced tracer methods that include modelling are set out. From the pathophysiological point of view the emphasis is on abnormalities in stress, brain metabolism in diabetes, eating and degenerative disorders. This book contains contributions from endocrinologists, physiologists, neurologists, psychoneuroendocrinOlogists, biophysicists, biochemists and experts in nutrition. This authorship represents a unique diversity of researchers who, for the first time, cover comprehensively the interaction between the nervous system and fuel homeostasis, both in health and disease. We hope this book will be an important source of information for both researchers and practicing clinicians. Mladen Vranic Suad Efendic Charles Hollenberg v ACKNOWLEDGEMENTS The Symposium from which this volume arose (University of Toronto, June 27-28, 1990) was the first Toronto-Stockholm symposium on Perspectives in Diabetes Research. These Symposia are organized triennially by the Banting and Best Diabetes Centre, University of Toronto and the Department of Endocrinology, Karolinska Institute, Stockholm.

The frontispiece, Leonardo da Vinci's drawing of the embryo in the womb, was chosen as a starting point for this book. It was Leonardo who in his notebooks and drawings combined artistic composition and accurate recording of the anatomy of the human body. Leonardo studied human anatomy in order to execute artistic drawings. His aim was to clarify form and function of human organs including reproductive organs. He followed up his extensive research with graphic representa tion and thereby initiated record keeping as a basis of scientific investigation. His records, accurate three-dimensional drawings, allowed others to reproduce his find ings and to test for correctness. Results could be updated and refined. Only after these steps can abnormalities be ascertained and defined as pathology. Though Leonardo was both artist and scientist, it is assumed that his anatomic drawings were used to improve his art, and thus scientific endeavor was at the service of his art. Anatomy, the offspring of science and art, is an integration of the two and became an accepted branch of the natural sciences. Although art and science continued to interact throughout the Renaissance, art was often placed in the service of science. In the course of history that followed, art and science in creasingly followed separate ways."

One of the most impressive advances in the field of neuroscience over the last decade has been the accumulation of data on plasticity and regeneration in the nervous system of mammals. The book represents the contribution of a qroup of neuroscientists to this rapidly expanding field, through a Conference organized by the Institute of Developmental Neuroscience and Aging (IDNA). The meeting was held in Torino, Italy during April 1990 in honor of a great pioneer in the field of Neuroembryology, Professor Guido Filogamo. His introduction of the concept of neuroplasticity has had a significant impact on the study of neurobiology. This volume is divided into six sections, each focusing on one of the subject areas covered during the meeting Molecular and Cellular Aspects of Central and Peripheral Nervous System Development; Hormones,* Growth Factors, Heurotransmi tters, Xenobiotics and Development; In Vivo and in Vitro models of Development; Development and Regulation of Glia; Regeneration; and Aging.

Rodents are the predominant experimental animals found in life-sciences research laboratories. The body temperature of a rodent is markedly affected by surgical, chemical or environmental manipulation. Because temperature regulation is controlled essentially by a 'holistic' regulatory system, meaning that its responses affect the activities of all other psychological and behavioural processes, it is clear that researchers working with rodents must be familiar with thermoregulatory physiology. With the help of extensive data tables and figures, this book explains the key facets of rodent thermal physiology, including neurological control and gender and intraspecies variations. There is a novel chapter on the effects of trauma, toxic chemicals and other factors. The book should therefore find use in government, academic or industrial laboratories whose researchers are working with rodents.

In this unique book, Sir Donald Harrison draws on his wide-ranging experience as a surgeon and comparative anatomist to produce an authoritative and detailed account of the anatomy and physiology of the mammalian larynx. His investigation of the larynx has involved the study of over 1400 specimens of mammalian larynges from around the world, as well as using data from his own clinical experiences. The comparative morphology of the larynx is discussed from a developmental and functional perspective and the involvement of the larynx in respiration, locomotion and vocalisation is highlighted. Throughout the book the relationship of structure to function is drawn out and the clinical relevance of features of the human larynx is emphasised. This book will be an invaluable reference for all researchers and clinicians involved in laryngology as well as for anatomists, zoologists and anaesthesiologists.

This monograph evolved from years of research into the auditory pathway and hearing of many species of marsupials. Its function is to give biologists, in par ticular neurobiologists, a broad description and review of what is known of the auditory sensory capacities and processing mechanisms in this large order of mammals. My initial interest in marsupials developed from collaborative work with Dr. Richard Gates at Monash and Melbourne Universities in the 1970s and by curiosity as to whether concepts about the auditory system was stimulated stemming from experiments mainly on domestic cats could be extended to mam mals of other orders. My subsequent interest in Australian marsupials, aroused by collaboration with Dr. John Nelson at Monash University in the 1980s and 1990s, concerned their auditory systems and behavior per se and not as primitive cousins of eutherians. More recently, I have collaborated with Dr. Bruce Masterton at Florida State University in studies of New World marsupials. His sad death in 1996 has robbed neurobiologists of one of our most provocative thinkers and hypothesis testers. I would like to thank the Department of Physiology at Monash University for making many facilities available to me, the National Health and Medical Research of Australia and the Australian Research Council for providing funds for Council research, and Jill Poynton and Michelle Mulholland, who illustrated this volume."

The symposium on Acoustical Signal Processing in the Central Auditory System which was held in Prague on September 4--7, 1996 was the third in a series organized in Prague, after the Neuronal Mechanisms of Hearing symposium in 1980 and Auditory Pathway - Structure and Function symposium in 1987. Approximately 100 scientists regis tered for the symposium and presented 82 separate papers and posters. The present vol ume contains 53 of these contributions, mostly presented at the symposium as invited review papers. Several essential changes occurred since the previous meeting in 1987. In auditory neuroscience, recently developed methods opened new horizons in the investigation of the structure and function of the central auditory pathway. Methods like c-fos tracing tech niques and monoclonal antibodies for neurotransmitters and their receptors, like the intro duction of electrophysiological recording from brain slices have made possible new insights into the function of individual neurons and their interconnections, particularly in the cochlear nuclei and in the superior olivary complex. Integrative approaches towards understanding the central auditory function started to dominate in the field. It is not easy at the present time to differentiate between purely morphological and neurochemical ap proaches; similarly electrophysiological approaches are accompanied inevitably by behav ioral and psychophysical studies. The understanding of human brain function advanced significantly during the last several years. mainly due to the contribution of magneto encephalography. positron emission tomography and functional nuclear magnetic reso nance imaging.

During the period August 5-9, 1992, and immediately preceding the 1992 Gordon Research Conference on Motile and Contractile Systems, the "Third International Conference on the Structure and Function of Ubiquitous Cellular Protein Actin" was held at the Emma Willard School in Troy, New York, under the title "ACTIN '92". This conference focused on the fundamental properties and cellular functions of actin and actin based microfilament systems. The first conference in this series was held in 1982, in Sydney, Australia, and hosted by Dr. Cristobal G. dos Remedios and Dr. Julian A. Barden, both from the University of Sydney (New South Wales, Austrailia). The second conference convened in Monza, Italy in June 1987, and was organized by Dr. Roberto Colombo, University of Milan (Italy). This third gathering of researchers devoted to the study of actin and actin-associated proteins was organized by Dr. James E. Estes, Albany Stratton V A Medical Center and Dr. Paul 1. Higgins, Albany Medical College, who were assisted by an Organizing Committee consisting of Dr. Edward D. Korn (National Heart, Lung and Blood Institute, NIH), Dr. Thomas P. Stossel (Massachusetts General Hospital), Dr. Fumio Matsumura (Rutgers University), and Dr. Stephen Farmer (Boston University). This meeting was dedicated to the many pioneering contributions of Professor Fumio Oosawa to the field of actin research.

This book includes articles relating to presentations given in a variety of forms (lectures, posters, contributions to round tables, software presentations) at the 5th International Biothermokinetics Meeting held in Bordeaux-Bombannes, September 23-26, 1992. The fact that not just lectures were considered for these proceedings reflects the aims of BTK meetings to instigate discussion, promote scientific cooperation and confront as many different ideas as possible with each other (at best heretical ones). BTK conferences have expanded more and more; 130 participants came to the 1992 meeting from 20 countries. It was therefore necessary to hold the round tables in parallel sessions. It is difficult to have an unbiased feeling of what should be selected as the salient features of the meeting. As the name suggests, Biothermokinetics embraces thermodynamic and kinetic approaches to experimental and theoretical investigations of biological processes, in particular at the cellular level. This "classical" point of view is mainly represented in the chapter "Thermodynamics and Kinetics of Transport Processes and Biological Energy Transduction."

The understanding of parallel processing and of the mechanisms underlying neural networks in the brain is certainly one of the most challenging problems of contemporary science. During the last decades significant progress has been made by the combination of different techniques, which have elucidated properties at a cellular and molecular level. However, in order to make significant progress in this field, it is necessary to gather more direct experimental data on the parallel processing occurring in the nervous system. Indeed the nervous system overcomes the limitations of its elementary components by employing a massive degree of parallelism, through the extremely rich set of synaptic interconnections between neurons. This book gathers a selection of the contributions presented during the NATO ASI School "Neuronal Circuits and Networks" held at the Ettore Majorana Center in Erice, Sicily, from June 15 to 27, 1997. The purpose of the School was to present an overview of recent results on single cell properties, the dynamics of neuronal networks and modelling of the nervous system. The School and the present book propose an interdisciplinary approach of experimental and theoretical aspects of brain functions combining different techniques and methodologies.

Birds and reptiles have long fascinated investigators studying hearing and the auditory system. The highly evolved auditory inner ear of birds and reptiles shares many characteristics with the ear of mammals. Thus, the two groups are essential in understanding the form and function of the vertebrate and mammalian auditory systems. Comparative Hearing: Birds and Reptiles covers the broad range of our knowledge of hearing and acoustic communication in both groups of vertebrates. This volume addresses the many similarities in their auditory systems, as well as the known significant differences about hearing in the two groups.

In Volume 12, eminent international ornithologists further elucidate endocrinological correlates of mating strategies and hormones and reproductive behavior; assess the value of the ''brood reduction hypothesis'' in explaining ''the paradox of hatching asynchrony''; and explore the validity and sensitivity of growth bands in feathers as an indication of nutritional condition and the use of feather banding in studying growth. Chapters are well supported with charts, maps, schematic diagrams, and photographs. Current Ornithology is the only English-language publication currently devoted exclusively to extensive reviews and synthesis of topics pertaining to all aspects of the biology of birds. Chapters fall under such diverse rubrics as ecology, evolution, behavior, phylogeny, behavioral ecology, anatomy and physiology, and conservation biology. All authors are leading authorities on their subjects, and each chapter is refereed by experts in the topics covered. Although all chapters focus primarily on birds, some topics, such as the social cognition of birds as compared to primates (Volume 13), have significant application to disciplines outside of ornithology. Current Ornithology aims to provide an accessible, up-to-date, accurate source of data and to contribute to conceptual generalization and unification across the biological sciences.

Studies have identified important families of proteins (denoted: heat shock or stress proteins, Hsps) which display an enhanced expression in response to heat shock or other physiological stresses. Besides the characterization of the genes encoding Hsp and the mechanisms of their induction, recent studies have concentrated on the function of these proteins. It was shown that the expression of Hsp protects the cell against different types of aggressions. In addition,Hsp can regulate essential biochemical processes in unstressed cells. For example, members of the Hsp60 and Hsp70 families act as ATP-binding proteins allowing the folding of nascent or denatured proteins as well as the assembly or disassembly of protein complexes. These observations have led to the discovery of the molecular chaperone concept (Ellis and Hemmingsen 1989). Amongst the proteins whose expression is up-regulated by heat shock or other types of stresses are the small stress proteins also denoted (sHsps, sHsp or sHSP). Small stress proteins encompass a large numbers of related proteins which are represented in virtually all organisms, including prokary- otes. These polypeptides share a structural domain, often referred to as the a-crystallin domain, common to the lens protein alpha-crystallin (Ingolia and Craig 1982;Wistow 1985). In addition to being increased in response to several types of stresses, the Hsp level is also upregulated during development and correlates with the differentiation and oncogenic status of the cell. In spite of the fact that sHsp can confer cellular protection against stresses,their molecular function has remained enigmatic for years.

The International Society for Arterial Chemoreception (ISAC) was founded in August 1988 during the 9th International Symposium on Arterial Chemoreception which was held at Park City, Utah, USA. ISAC was established with the aim of providing a framework to support the increasing number of investigators from a wide variety of disciplines (anatomists, pathologists, respiratory physiologists and clinicians, high altitude physiologists, biochemists, biophysicists, physiologists and pharmacologists) who share a common interest in arterial chemoreception. ISAC took over the co-ordination of the international chemoreceptor meetings, with the membership deciding the venue for forthcoming meetings. During the Park City symposium Dublin was selected to host the 1993 meeting, under the Presidency of Professor Ronan O'Regan. The 12th International Meeting on Arterial Chemoreception, which was held in Dublin in August 1993, was acclaimed as a great success by all those present. The delegates not only shared in a wide-ranging feast of chemoreceptor based science, they had plenty of opportunity during the meeting for renewing acquaintances and establishing new friendships. The location for the meeting at University College Dublin's modem Belfield campus helped to promote such interaction, and the social programme was outstanding.

Understanding how the brain works is undoubtedly the greatest challenge for human intelligence and one of the most ambitious goals of contemporary science. We are certainly far from this goal, but significant advancements in several fields of Neuroscience and Neurobiology are being obtained at an increasing pace. The NATO ASI School in Neurobiology, held in Erice May 2-12,1995, as the 23rd Course of the International School of Biophysics, provided an update on three basic topics: Biophysics and Molecular Biology ofIon Channels, Sensory Transduction, and Higher Order Functions. Current knowledge on these subjects was covered by formal lectures and critical discussions between lecturers and participants. This book collects original contributions from those scientists who attended the School. Many students presented their results in poster sessions, steering lively informal discussions. A selection of these contributions is also included. A major portion of the program of the School was devoted to a general overview of current trends of thought and experimental approaches in neurobiology, emphasising the importance of understanding molecular aspects of the elementary events underlying sensory transduction and processing in the nervous system, without indulging however in a pure reductionistic view of such complex phenomena. Recent studies of molecular biology and the electrophysiology of heterologously expressed ionic channels, have shed new light on the molecular mechanisms underlying ionic permeation of excitable membranes and its regulation by physical and chemical parameters.