Cambridge University PressCambridge, UKEPHExperimental PhysiologyExp. Physiol.0958-067083417170958-0670(19987)83:4S0958067098017175449460The Physiological Society 1998INTRACELLULAR Mg2+ REGULATION IN VOLTAGE-CLAMPED HELIXA SPERSA NEURONES MEASURED WITH MAG-FURA-2 AND Mg2+-SENSITIVE MICROELECTRODESHELEN J.KENNEDYDepartment of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UKHelen J. Kennedy: helen.kennedy@bristol.ac.ukThe extrusion mechanism for intracellular Mg2+ was investigated in voltage-clamped snail neurones using Mg2+-sensitive microelectrodes and mag-fura-2. The intracellular free magnesium ion concentration ([Mg2+]i) of snail neurones voltage clamped to -60 mV was estimated to be 0·57 ± 0·06 mM (mean ± S.E.M.; n = 12) using Mg2+-sensitive microelectrodes and 0·62 ± 0·05 mM (n = 15) using mag-fura-2 . Raising extracellular MgCl2 from 5 to 20 mM caused an average increase in [Mg2+]i of 0·25 ± 0·04 mM (n = 7). In three experiments, removing extracellular MgCl2 caused an average decrease in [Mg2+]i of 0·1 mM. Replacing extracellular Na+ with N-methyl-D-glucamine (NMDG) caused a rise in [Mg2+]i of 1·8 ± 0·5 mM (n = 7); [Mg2+]i recovered to resting levels when extracellular Na+ was restored. Iontophoretic injections of MgCl2 were used to raise [Mg2+]i. The rate of recovery from such increases in [Mg2+]i (calculated from the slope of the recovery) was inhibited by 85-100 % (n = 5) in the absence of extracellular Na2+ compared with control conditions. Raising extracellular Ca2+ from 7 to 35 mM caused a reversible rise in [Mg2+]i of 0·4 ± 0·05 mM (mean ± S.E.M., n = 7). It was concluded that in snail neurones the main mechanism for [Mg2+]i extrusion is a Na+-Mg2+ exchanger which may be partially inhibited be high extracellular Ca2+ concentrations.

Cambridge University PressCambridge, UKEPHExperimental PhysiologyExp. Physiol.0958-067083417240958-0670(19987)83:4S0958067098017242469480The Physiological Society 1998THE ROLE OF NITRIC OXIDE IN THE CONTROL BY THE VAGAL NERVES OF THE HEART OF THE FERRETKELLYCONLONTANYACOLLINSCECILKIDDDepartment of Biomedical Sciences, Medical School, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UKCecil Kidd: c.kidd@abdn.ac.ukThis study focuses on the potential role for nitric oxide on the actions of the parasympathetic innervation to the heart. Earlier, we showed that the nitric oxide synthase (NOS) inhibitor N[omega]- nitro-L-arginine methyl ester (L-NAME) reduced the bradycardia induced by stimulation of vagal efferent motor fibres and that these effects are reversible through administration of the NOS substrate L-arginine. In the present study, we show that D-arginine does not reverse the effects of the inhibitors and confirm that they are reversed by L-arginine. Another NOS inhibitor, NG -nitro-L-arginine (L-NOARG), produced similar effects which were not reversed by L-arginine. In an examination of the effect of increasing NO availability with the NO donor sodium nitroprusside the vagally induced bradycardia was enhanced at all frequencies tested. In a separate series, the effects of NOS inhibitors and NO donors on the dromotropic actions of the vagus were examined. The NOS inhibitor L-NAME, reduced the increase in atrio-ventricular conduction delay normally induced by efferent vagal stimulation at all frequencies tested both in the 'paced' and 'unpaced' heart. Further, sodium nitroprusside enhanced this delay. Overall the study indicates that NO has an important facilitatory role on both the chronotropic and dromotropic actions of the vagus nerve on the heart and that NO may be a rate-limiting factor in the cardiac responses to vagal stimulation.

Cambridge University PressCambridge, UKEPHExperimental PhysiologyExp. Physiol.0958-067083417140958-0670(19987)83:4S095806709801714X481487The Physiological Society 1998THE INFLUENCE OF STREPTOZOTOCIN-INDUCED DIABETES AND THE ANTIHYPERGLYCAEMIC AGENT METFORMIN ON THE CONTRACTILE CHARACTERISTICS AND THE MEMBRANE POTENTIAL OF THE RAT DIAPHRAGMMICHELLEMcGUIREMARYMacDERMOTTDepartment of Physiology, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, IrelandMary MacDermott: mmacderm@rcsi.ieAfter 2 months of streptozotocin-induced diabetes in rats, the membrane potential of the diaphragm muscle when measured in vitro at 30¡C was unchanged but the tetanic tension, the half-relaxation time of the isometric twitch and the fatigue resistance were each reduced. Treatment of the diabetic rats with the antihyperglycaemic agent metformin prevented the decrease in half-relaxation time and the greater degree of fatigue in the diaphragms. The possibility that changes in H+ and cyclic AMP concentrations in the diabetic muscles contributed to the decreased contractile function and that metformin acted by attenuating these changes is discussed.

Cambridge University PressCambridge, UKEPHExperimental PhysiologyExp. Physiol.0958-067083417270958-0670(19987)83:4S0958067098017278489501The Physiological Society 1998GLUCOSE 6-PHOSPHATE ALTERS RAT SKELETAL MUSCLE CONTRACTILE APPARATUS AND SARCOPLASMIC RETICULUM FUNCTIONJAY H.WILLIAMSCHRISTOPHER W.WARDESPEN E.SPANGENBURGREAGANNELSONSTASINOSSTAVRIANEASGARY A.KLUGMuscular Function Laboratory. Department of Human Nutrition, Foods and Exercise Virginia Polytechnic Institute and State University, Blacksburg, VA 24061Department of Exercise and Movement Studies University of Oregon, Eugene, OR 97403, USAJay H. Williams: jhwms@vt.eduWe investigated the effects of glucose 6-phosphate (G6P) on skeletal muscle contractile apparatus and sarcoplasmic reticulum (SR) function. Using rat extensor digitorum longus fibres, the presence of 5 mM G6P decreased the Ca2+ sensitivity of both force production and actomyosin ATPase (AM-ATPase) activity. Conversely, maximal Ca2+-activated force was unaffected while maximal AM-ATPase activity was increased by 37 %. In SR vesicles isolated from rat gastrocnemius, G6P markedly altered Ca2+ handling. It increased Ca2+-stimulated Ca2+-ATPase activity but depressed the net rate of Ca2+ uptake. This latter effect appears to be due to G6P-stimulated Ca2+ release. When G6P was added to Ca2+-loaded vesicles, a small, transient release of Ca2+ was elicited. In addition, G6P lowered the threshold for Ca2+-induced Ca2+ release but depressed the net rates of both AgNO3- and caffeine-induced releases. It is possible that the accumulation of G6P during muscular activity may adversely affect muscle force production and contribute to the fatigue process via its action on the contractile apparatus and SR.

Cambridge University PressCambridge, UKEPHExperimental PhysiologyExp. Physiol.0958-067083417040958-0670(19987)83:4S0958067098017047545556The Physiological Society 1998AUTONOMIC CONTROL OF SUBMANDIBULAR PROTEIN SECRETION IN THE ANAESTHETIZED CALFP. A.CALVERTP. M.HECKA. V.EDWARDSPhysiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UKA. V. Edwards: ave1000@cus.cam.ac.ukThe autonomic control of submandibular secretion has been investigated in fully weaned, anaesthetized calves 7 weeks after birth. Stimulation of the parasympathetic (chorda-lingual) innervation invariably produced a flow of saliva, the rate of which was frequency dependent over the range 2-8 Hz continuously. Neither the rate of flow nor the output of protein was enhanced by stimulating in bursts at relatively high frequencies. Stimulation of the sympathetic innervation (20 Hz for 1 s at 10 s intervals) alone produced a much slower flow of saliva but with a considerably higher protein content. Stimulation of both together produced no greater flow of saliva than occurred with either alone at the lower frequencies (2 and 4 Hz) but there was a pronounced synergy in respect of the secretion of protein. Following pre-treatment with propranolol (1·0 mg kg-1 I.V.), during on-going chorda-lingual stimulation at 4 Hz, intra-arterial injections of 1 nmol of either vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase activating peptide (PACAP) elicited an increase in the flow and protein output of about the same order of magnitude. Calcitonin gene-related peptide (CGRP) also produced these same effects with roughly half the efficacy of VIP and PACAP but substance P had no detectable effect. It is concluded that VIP, PACAP and possibly CGRP are candidates for neurotransmitters with a role in the control of secretion in this gland.

Cambridge University PressCambridge, UKEPHExperimental PhysiologyExp. Physiol.0958-067083403990958-0670(19987)83:4S0958067098003996Book Review571572The Physiological Society 1998Eckert Animal Physiology: Mechanisms and Adaptations, 4th edn. By D. Randall, W. Burggren and K. French. Pp. 723. W. H. Freeman and Company, 1997. £28.95 hardback. ISBN 0 716 6724146.MICHAEL J.McKINLEYI am still puzzling over such questions as to what is the largest object caught in a spider's web and what are the limitations to building larger webs? Or, what might be the selective forces that have operated on the evolution of aglomerular kidneys that has occurred in a few marine teleost species? These are just a couple of the thought-provoking questions that are posed liberally throughout the latest (4th) edition of Eckert's Animal Physiology that has been revised by Randall, Burggren and French. For those students and teachers who found the earlier editions of this book instructional and a valuable resource, its extensive revision and expansion will be received with enthusiasm. The authors have produced an excellent textbook of animal physiology. The animal kingdom is so diverse, one wonders how such a book can be confined to 700 pages. The aim of the authors has been to carefully elucidate the general physiological principles and physico-chemical laws which govern all forms of animal life and then to illustrate these laws with examples of adaptations drawn from a wide range of organisms. This aim has been largely fulfilled and the authors are to be congratulated on their revision.