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Cell signalling
TiPS - July 1990 [Vol. 121
300
Cardiac confusion Antiarrhythmic Drugs (Handbook of Experimental Pharmacology, Vol. 89) edited by E. M. Vaughan Williams, Springer Verlag, 1989. DM 480.00 (v + 650 pages) ISBN 3 540 19239 5 This is a valuable book in which many of the leading workers review a particularly wide and carefully selected range of pharmacological, clinical and other work on antiarrhythmic drugs. Six introductory chapters (including a necessary assessment of the successes and limitations of drug therapy in arrhythmias) are followed by 24 chapters on individual aspects following the standard classification of Vaughan Williams. The chapters contain lists of references that will be one of the most valuable features of the book, which researchers in the field will surely regard as a necessary addition to their libraries. It is therefore disappointing that the preliminary treatment of the electrophysiological basis of cardiac rhythm is confused and confusing. It is incorrect, for example, to write (p. 36) in 1989 that ‘The nature of the current responsible for the slow diastolic depolarization [in Purkinje fibres] is still controversial’ when it has been widely agreed for some years that this current is the same as the hyperpolarizing-activated inward current in the sinus node. It is particularly inappropriate to persist with this confusion (which in was, of course, widespread 1980-1982 when the major reinterpretation of pacemaker currents occurred) since the reinterpretation is agreed even by those who proposed the original iK2 hypothesis. Indeed it was one of those authors (myself) who collaborated with DiFrancesco to demonstrate the complete compatibility of the new theory with all the previous experimental work. Does it matter, or should we leave these issues to the historians? It matters now because that work makes it possible easily to reinterpret all the pharmacological work done using the old theory indeed it must be rare that two competing theories have been so completely mapped on to each other in this way. A good example is the activation curve shift pro-
duced by adrenaline (not even referred to in this book), which is one of the major features of the chronotropic action of P-adrenoceptor antagonists and is a subject of very active current interest, being studied using patch-clamp methods. Another is the interpretation of the actions of very low levels of cardiac glycosides; contrary to the implication in the Preface (p. viii), this is actually reinforced by the reinterpretation of iK2 as if since the mapping of the theories makes total sense of the precise dependence of the ‘reversal potential’ on the Kf ion gradient. In any case, the controversy over the actions of low levels of glycosides never depended solely on electrophysiological evidence: the best evidence for a second action (and binding site) at low concentrations came from
Signalling textbook Cell Signalling by N. Press, (vii + X hbk,
G. Morgan, Open University 1989. E35.00 hbk, E14.99 pbk 203 pages) 1SBN 0 335 15820 0 335 15819 6 pbk
The field of cellular signalling is currently an area of intense activity, and for many undergraduates or research students the vast volume of publications in the field may seem impenetrable. Cell Signalling is an attempt to produce a comprehensive introduction to the mechanisms of hormonal communication. The book is largely devoted to the generation of second messengers and their effector systems within non-excitable cells. There is relatively little discussion of how the intracellular messengers affect the biochemistry of the cells. It provides discussion of receptors and their regulation, the role of G proteins as signal transducers, the generation of cyclic nucleotides and their effecters, PI turnover and Ca2+ mobilization, insulin and growth factor receptors, arachidonic acid and eicosanoid production, and a discussion of the role of protein phosphorylation/dephosphorylation in cell regulation. The book also helps to give an integrated picture of cellular signalling by discussing how different signal transduction mech-
work on isolated ATPases. There is a very general point to be made here. Reinterpretations, sometimes dramatic (as with Eccles’s famous conversion to the theory of chemical transmission), sometimes gradual (as with the painstaking efforts to unravel the complexity of the second inward current), are the essence of scientific advance. They are not necessarily synonymous either with ‘confusion’ or with ‘controversy’. At best, as with the reinterpretation of iK2, the result is to make sense of a previously confused and awkward set of experimental deviations. The result is greater clarity, which must make the work of pharmacologists easier. DENIS
NOBLE
Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX2 3PT, UK.
anisms interact by, for example, synergism between protein kinase C and Ca2+, and activation of adenylyl cyclase by Ca2+. Simple illustrations help to clarify the ideas discussed. As well as discussing current ideas concerning cellular signalling, the book often points out the situations where the full facts are not yet known and attempts to give a plausible explanation on the basis of current information. The book will probably be a useful reference for research workers as the author has provided many biochemical details such as molecular weights, K, and Kd values, and stoichiometries. By comparison with a more general textbook such as chemistry by L.. Stryer (W.BiiI Freeman), Cell Signalli)zg has considerably more detail. It is not however, as readable as the former book, mainly because the chapters are subdivided into titled paragraphs which often do not flow. There are several irritating typographical errors. This book would be valuable reading for many biology students studying cellular communication, and each chapter has a concise reference list which would be a useful starting point for further reading. MARTIN
BOOTMAN
AFRC Laboratory of Molecular S&walling, Department of Zoology, Downing Street, Cambridge CR2 3E], UK.
300
Cardiac confusion Antiarrhythmic Drugs (Handbook of Experimental Pharmacology, Vol. 89) edited by E. M. Vaughan Williams, Springer Verlag, 1989. DM 480.00 (v + 650 pages) ISBN 3 540 19239 5 This is a valuable book in which many of the leading workers review a particularly wide and carefully selected range of pharmacological, clinical and other work on antiarrhythmic drugs. Six introductory chapters (including a necessary assessment of the successes and limitations of drug therapy in arrhythmias) are followed by 24 chapters on individual aspects following the standard classification of Vaughan Williams. The chapters contain lists of references that will be one of the most valuable features of the book, which researchers in the field will surely regard as a necessary addition to their libraries. It is therefore disappointing that the preliminary treatment of the electrophysiological basis of cardiac rhythm is confused and confusing. It is incorrect, for example, to write (p. 36) in 1989 that ‘The nature of the current responsible for the slow diastolic depolarization [in Purkinje fibres] is still controversial’ when it has been widely agreed for some years that this current is the same as the hyperpolarizing-activated inward current in the sinus node. It is particularly inappropriate to persist with this confusion (which in was, of course, widespread 1980-1982 when the major reinterpretation of pacemaker currents occurred) since the reinterpretation is agreed even by those who proposed the original iK2 hypothesis. Indeed it was one of those authors (myself) who collaborated with DiFrancesco to demonstrate the complete compatibility of the new theory with all the previous experimental work. Does it matter, or should we leave these issues to the historians? It matters now because that work makes it possible easily to reinterpret all the pharmacological work done using the old theory indeed it must be rare that two competing theories have been so completely mapped on to each other in this way. A good example is the activation curve shift pro-
duced by adrenaline (not even referred to in this book), which is one of the major features of the chronotropic action of P-adrenoceptor antagonists and is a subject of very active current interest, being studied using patch-clamp methods. Another is the interpretation of the actions of very low levels of cardiac glycosides; contrary to the implication in the Preface (p. viii), this is actually reinforced by the reinterpretation of iK2 as if since the mapping of the theories makes total sense of the precise dependence of the ‘reversal potential’ on the Kf ion gradient. In any case, the controversy over the actions of low levels of glycosides never depended solely on electrophysiological evidence: the best evidence for a second action (and binding site) at low concentrations came from
Signalling textbook Cell Signalling by N. Press, (vii + X hbk,
G. Morgan, Open University 1989. E35.00 hbk, E14.99 pbk 203 pages) 1SBN 0 335 15820 0 335 15819 6 pbk
The field of cellular signalling is currently an area of intense activity, and for many undergraduates or research students the vast volume of publications in the field may seem impenetrable. Cell Signalling is an attempt to produce a comprehensive introduction to the mechanisms of hormonal communication. The book is largely devoted to the generation of second messengers and their effector systems within non-excitable cells. There is relatively little discussion of how the intracellular messengers affect the biochemistry of the cells. It provides discussion of receptors and their regulation, the role of G proteins as signal transducers, the generation of cyclic nucleotides and their effecters, PI turnover and Ca2+ mobilization, insulin and growth factor receptors, arachidonic acid and eicosanoid production, and a discussion of the role of protein phosphorylation/dephosphorylation in cell regulation. The book also helps to give an integrated picture of cellular signalling by discussing how different signal transduction mech-
work on isolated ATPases. There is a very general point to be made here. Reinterpretations, sometimes dramatic (as with Eccles’s famous conversion to the theory of chemical transmission), sometimes gradual (as with the painstaking efforts to unravel the complexity of the second inward current), are the essence of scientific advance. They are not necessarily synonymous either with ‘confusion’ or with ‘controversy’. At best, as with the reinterpretation of iK2, the result is to make sense of a previously confused and awkward set of experimental deviations. The result is greater clarity, which must make the work of pharmacologists easier. DENIS
NOBLE
Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX2 3PT, UK.
anisms interact by, for example, synergism between protein kinase C and Ca2+, and activation of adenylyl cyclase by Ca2+. Simple illustrations help to clarify the ideas discussed. As well as discussing current ideas concerning cellular signalling, the book often points out the situations where the full facts are not yet known and attempts to give a plausible explanation on the basis of current information. The book will probably be a useful reference for research workers as the author has provided many biochemical details such as molecular weights, K, and Kd values, and stoichiometries. By comparison with a more general textbook such as chemistry by L.. Stryer (W.BiiI Freeman), Cell Signalli)zg has considerably more detail. It is not however, as readable as the former book, mainly because the chapters are subdivided into titled paragraphs which often do not flow. There are several irritating typographical errors. This book would be valuable reading for many biology students studying cellular communication, and each chapter has a concise reference list which would be a useful starting point for further reading. MARTIN
BOOTMAN
AFRC Laboratory of Molecular S&walling, Department of Zoology, Downing Street, Cambridge CR2 3E], UK.