Table Of ContentCell Physiology Sourcebook
Essentials of Membrane Biophysics
Fourth Edition
Nicholas Sperelakis
Department of Physiologyand Biophysics,
College of Medicine, University of Cincinnati,
Cincinnati, Ohio
AMSTERDAMlBOSTONlHEIDELBERGlLONDONlNEWYORKlOXFORDlPARIS
SANDIEGOlSANFRANCISCOlSINGAPORElSYDNEYlTOKYO
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First edition1995
Second edition 1998
Third edition 2001
Fourth edition 2012
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Dedication
This book is dedicated to Planet Earth and to all those (deceased), Christine M., Sophia A., Thomas A., and
organizationsthatareworkingtirelesslytosaveandprotect Anthony J., daughter-in-law Sherri, and grandchildren
the environment, to stop pollution of our oceans, lakes, Demetra, GregoryandNina-Nicole.
rivers, drinking water, air, and soil, to preserve the farm- A special thanks to David Magnuson, M.D., Chairman
lands,tostabilizeworldpopulation,toprotectandpreserve of Pediatric Surgery at Cleveland Clinic, for his great
wildlife,topromoteanimalwelfare,andtofightforhuman dedication, skills, wisdom and humanity. Efharisto para
rights aroundtheglobe. poli, aka “EU´XarIsTuparά pOlU´”.
Ialsowanttoacknowledgetheloveandsupportofmy
family: my wife Dolores and children Mark Demitri
In Memoriam
DrHugoGonzalez-SerratospassedawayonApril1,2011. achievedgreat recognition as a top scientist in the field of
Hugo was Professor of Physiology at the University of musclephysiology.Hewill begreatlymissedby allofus.
Maryland in Baltimore. He was a graduate student of Professor Gonzalez-Serratos was a contributing author to
ProfessorAndrewF.Huxley,Nobellaureate,atUniversity this book. May his memory be eternal!
College London in the mid-1960s. Dr Gonzalez-Serratos
xi
Contributors
Francisco J. Alvarez-Leefmans MD, PhD, Professor, Darrell Fleischman, Adjunct Associate Professor,
Department of Pharmacology and Toxicology, Department of Biochemistry and Molecular Biology,
Boonshoft School of Medicine, Wright State Boonshoft School of Medicine, Wright State
University, Dayton, Ohio, USA University, Dayton, Ohio, USA
Clive M. Baumgarten, Professor of Physiology and Michael S. Forbes Ph.D., Department of Pediatrics,
Biophysics, Biomedical Engineering and Medicine University of Virginia School of Medicine,
(Cardiology), School of Medicine, Virginia Charlottesville, Virginia, USA
Commonwealth University, Richmond
Kenneth W. Foster, Professor, Physics Department,
KennethM.Blumenthal,ProfessorandChairman,SUNY Syracuse University, Syracuse, New York, USA
Department of Biochemistry, School of Medicine and
Jeffrey C. Freedman, Associate Professor, Neuroscience
Biomedical Sciences, Buffalo, New York, USA
and Physiology, SUNY Upstate Medical University,
John H.B. Bridge, Research Professor of Medicine, Syracuse, New York, USA
Division of Cardiology, University of Utah Health
Andrew S. French, Professor of Physiology and
Sciences Center, Nora Eccles Harrison Cardiovascular
Biophysics, Department of Physiology and
Research and Training Institute, University of Utah,
Biophysics, Halifax, Nova Scotia, Canada
CVRTI, Salt Lake City, Utah, USA
Nicole Gallo-Payet, Professor and Research Chair of the
Bruce A. Carlson, Washington University, St Louis, Faculty of Medicine and Health Sciences,
Missouri, USA Departments of Endocrinology, and Medicine,
UniversityofSherbrooke,Sherbrooke,Quebec,Canada
Laura Conforti, Department of Internal Medicine,
University of Cincinnati, Cincinnati, Ohio, USA Hugo Gonzalez-Serratos, Professor, Physiology,
University of Maryland, School of Medicine,
John R. Dedman, Professor and Ohio Eminent Scholar,
Baltimore, Maryland, USA
Department of Cancer & Cell Biology, Department of
Molecular and Cell Biology, University of Cincinnati, Anthony L. Gotter, Division of Human Genetics, The
Cincinnati, Ohio, USA Children’s Hospital of Philadelphia and the Joseph
Stokes Jr Research Institute, Philadelphia,
Neil D. Detweiler, Department of Pharmacology and
Pennsylvania, USA
Toxicology, University of Arkansas for Medical
Sciences, Little Rock, Arkansas, USA Michael S. Grace, Associate Professor, Biological
Sciences Department, College of Science, Florida
Istvan Edes, Institute of Cardiology, University of
Institute of Technology, Melbourne, Florida, USA
Debrecen, Debrecen, Hungary
Steven M. Grassl, Associate Professor, Pharmacology,
Robert A. Farley PhD, Professor Physiology and
State University of NY Upstate Medical University,
Biophysics, Biochemistry and Molecular Biology,
Syracuse, New York, USA
Departments of Physiology and Biophysics, and
Biochemistry and Molecular Biology, Keck School of Dennis W. Grogan, Professor, Department of Biological
Medicine, University of Southern California, Los Sciences, University, College of Arts and Sciences,
Angeles, California, USA University of Cincinnati, Cincinnati, Ohio, USA
Joseph J. Feher PhD, Professor of Physiology and J. Woodland Hastings, Professor of Natural Sciences,
Biophysics, School of Medicine, Virginia Department of Molecular and Cellular Biology,
Commonwealth University, Richmond, Virginia, USA Harvard University, Cambridge, Massachusetts, USA
xiii
xiv Contributors
Judith Heiny, Associate Professor, Department of Gerhard Meissner, Professor, Departments of Cell and
Molecular and Cellular Physiology, University of Molecular Physiology, and Biochemistry and
Cincinnati, Cincinnati, Ohio, USA Biophysics, The University of North Carolina at
Chapel Hill School of Medicine, Chapel Hill, North
Aldebaran M. Hofer, Associate Professor of Surgery &
Carolina, USA
Research Health Scientist, VA Boston Healthcare
System and the Department of Surgery, Brigham and Stan Misler, Associate Professor, Internal Medicine,
Women’s Hospital and Harvard Medical School, Cell Biology and Physiology, Washington University
Massachusetts, USA in St Louis School of Medicine, St Louis, Missouri,
USA
Atsushi Inanobe,Department ofPharmacology,Graduate
School of Medicine and The Center for Advanced Catherine E. Morris, Senior Scientist, Neuroscience,
Medical Engineering and Informatics, Osaka Ottawa Hospital Research Institute; Professor,
University, Osaka, Japan Department of Medicine, Division of Neurology,
University of Ottawa, Ottawa, Ontario, Canada
MarciaA.Kaetzel,DepartmentofCancerandCellBiology,
University of Cincinnati, Cincinnati, Ohio, USA MichelaOttolia,DepartmentofPhysiology,Cardiovascular
Research Laboratories, David Geffen School of
Robert S. Kass, Alumni and David Hosack Professor of
Medicine at UCLA, Los Angeles, California, USA
Pharmacology and Chair, Columbia University
College of Physicians and Surgeons, New York, USA Richard J. Paul, Professor, Director, PhD Program in
Systems Biology and Physiology, Department of
Sujay V. Kharade, Department of Pharmacology and
Molecular and Cellular Physiology, College of
Toxicology, University of Arkansas for Medical
Medicine, University of Cincinnati, Cincinnati, Ohio,
Sciences, Little Rock, Arkansas, USA
USA
Takeshi Kobayashi, Assistant Professor, Department of
Asif R. Pathan, Department of Pharmacology and
Cellular Physiology and Signal Transduction,
Toxicology, University of Arkansas for Medical
Sapporo Medical University School of Medicine,
Sciences, Little Rock, Arkansas, USA
Sapporo, Japan
MarcelDanielPayet,Professor,DepartmentofPhysiology
EvangeliaG.Kranias,Chair,DepartmentofPharmacology
and Biophysics, Faculte´ de Me´decine, Universite´ de
& Cell Biophysics, Distinguished University Professor,
Sherbrooke, Sherbrooke, Quebec, Canada
Co-Director, Cardiovascular Center of Excellence,
Department of Pharmacology and Cell Biophysics, Matthew Pincus, Professor, Clinical Pathology, SUNY
University of Cincinnati, Cincinnati, Ohio, USA Downstate Medical Center in Brooklyn; Chief,
Department of Pathology & Laboratory Medicine,
Yoshihisa Kurachi, Department of Pharmacology,
New York Harbor VA Medical Center, Brooklyn,
Graduate School of Medicine and The Center for
New York, USA
Advanced Medical Engineering and Informatics,
Osaka University, Osaka, Japan Tracy J. Pritchard, Department of Pharmacology and
Cell Biophysics, University of Cincinnati, Cincinnati,
Stephen Lambert, Associate Professor of Medicine,
Ohio, USA
College of Medicine, University of Central Florida,
Health Sciences Campus at Lake Nona, Orlando, Robert W. Putnam, Professor, Department of
Florida, USA Neuroscience, Cell Biology and Physiology, Boonshoft
School of Medicine, Wright State University, Datyton,
Michael Levandowsky, Research Scientist, Adjunct
Ohio, USA
Professor of Biology, Haskins Laboratories, Pace
University, New York, USA Seth Robey, Department of Pharmacology, College of
Physicians and Surgeons, Columbia University, NY,
Simon Rock Levinson, Professor, Department of
New York, USA
Physiology and Biophysics, University of Colorado
School of Medicine, Aurora, Colorado, USA Stephen D. Roper, Professor, Department of Physiology
and Biophysics, University of Miami Miller School
DanielC.Marcus,ProgramDirector,KSUCOBREgrant;
of Medicine, Miami, Florida, USA
Professor, Anatomy and Physiology, College of
Veterinary Medicine, Kansas State University, Nancy J. Rusch, Professor and Chair, Department of
Manhattan, Kansas, USA Pharmacology and Toxicology, University of Arkansas
Contributors xv
College of Medicine, University of Arkansas for Pa¨iviH.Torkkeli,ProfessorofPhysiologyandBiophysics,
Medical Sciences, Little Rock, Arkansas, USA Department of Physiology and Biophysics, Dalhousie
University, Halifax, Nova Scotia, Canada
KevinJ.Sampson,DepartmentofPharmacology,College
of Physicians and Surgeons, Columbia University, NY, Natalia S. Torres, Nora Eccles Harrison Cardiovascular
New York, USA Research and Training Institute, University of Utah,
Salt Lake City, Utah, USA
William A. Sather, Associate Professor, Department of
Pharmacology, University of Colorado Denver, Kenneth R. Tovar, Vollum Institute, Oregon Health and
Aurora, Colorado, USA Science University, Portland, Oregon, USA
Nicholas Sperelakis, Department of Physiology Richard D. Veenstra, Department of Pharmacology,
and Biophysics, College of Medicine, University of SUNY Upstate Medical University, Syracuse, New
Cincinnati, Cincinnati, Ohio, USA York, USA
Anup K. Srivastava, Department of Pharmacology and Gordon M. Wahler, Professor, Physiology, Midwestern
Toxicology, University of Arkansas for Medical University, Downers Grove, Illinois, USA
Sciences, Little Rock, Arkansas, USA
Gary L. Westbrook, Senior Scientist and Co-Director,
Janusz B. Suszkiw, Professor, Department of Molecular Vollum Institute Dixon, Professor of Neurology
and Cellular Physiology, University of Cincinnati, Oregon Health and Science University Portland, OR
Cincinnati, Ohio, USA USA
Timothy C. Tricas, Professor, Department of Zoology & Hisashi Yokoshiki, Associate Professor, Department of
Hawaii Institute of Marine Biology, University of Cardiovascular Medicine, Hokkaido University
Hawaii at Manoa, Honolulu, Hawaii, USA Graduate School of Medicine, Sapporo, Japan
Noritsugu Tohse, Professor, Department of Cellular Anita L. Zimmerman, Professor and Vice Chair,
Physiology and Signal Transduction, Sapporo Molecular Pharmacology, Physiology and
Medical University School of Medicine, Sapporo, Biotechnology, Brown University, Providence, Rhode
Japan Island, USA
Foreword
Foreword to the First Edition
ItwaskindandgenerousofmyfriendNicholasSperelakis suggested that it might be replaced by “the study of those
to relate this excellent book so closely to my own, A features of life that appear to be common to all forms.”
Textbook of General Physiology. In the preface to the first Whateverdefinition we choose, however, it is ofimmense
editionofmybook,Ihadexpressedthehopethatitmight satisfactiontomethatthisnewbook,essentially,hasbeen
be compared with Bayliss’ Principles of General Physi- fitted into the same sectional headings that I employed in
ology.Ifthiscomparisonisvalid,itisveryappropriatethat my ownbook.
the present book be organized and partly written by one If I may be permitted to reminisce further, I have
who is, along with Sir William Bayliss and myself, asso- wonderedfrequentlyhowasinglescientist,activelyengaged
ciated with University College London (Professor Sper- inresearch,couldwriteanewbookofsuchwidescope.The
elakishavingspentasabbaticalyearthere).Itisapleasure answeristhatIwrotethebookduringthe2yearsimmedi-
to recall that it was there that I first met Nicholas, and I ately following the end of World War II. Thus, for several
rememberdiscussinghispioneeringstudyonthepotentials yearseinGreatBritainforasmanyas10yearseverylittle
across the crystalline lens ofthe eye. original academic physiology and new research had been
ForreasonsthatIthinkbearnorelationtoitsscope,this published. This made it possible to survey the original
book has a different title; I presume it is because the literatureofalengthyperiodwithoutbeingoverwhelmedby
distinction between “ordinary” and “general” physiology a rapid succession of new discoveries that would have
hasbecomesufficientlyblurredtodemandsomethingmore renderedmytasknearlyimpossible,afatesimilartothatof
appropriate.ThedefinitionofgeneralphysiologythatIhad Sisyphus.Today,thistaskwouldbeimpossible,anditonly
proposed in the preface to the first edition of my textbook surprises me that Nicholas has been able to produce this
was“thestudyofthoseaspectsoflivingmaterialthatshow magnificentbookwithsofewcollaborators.
someimmediateprospectofbeingdescribedintermsofthe
known laws of physics and chemistry.” Later, I had Hugh Davson
misgivingsastothenarrownessofthisdefinition,andIthen 1995
xvii
Foreword
Foreword to the Second Edition
In his Foreword to the first edition of the Cell Physiology extensive revisions and the new material in the second
Sourcebook, Hugh Davson established it as the lineal edition raise it toa newlevel.
descendent of his own well-known and highly respected Cell physiology, an area of central importance in
work The Textbook of General Physiology. The second biology, has grown out of a number of more traditional
editionoftheCellPhysiologySourcebook,againeditedby fields,andasaresult,theliteraturecontinuestobewidely
Nicholas Sperelakis, continues in this same tradition. dispersed. The great value of the Cell Physiology Source-
Although the first edition was enthusiastically receivedby bookisthatitgatherstogetherunderasinglecoverabroad
the cell physiology community because of its depth and rangeofup-to-datechaptersthat,takentogether,definethe
breadth of coverage, considerable important progress has field.Thevariouschaptersexhibitauniformityofstyleand
been made in this rapidly developing area since its publi- levelofpresentationthatareacredittotheeditor.Because
cation. The second edition deals with these new develop- of this and the scope and clarity of the presentations, this
ments by a thorough reworking of topics and by the book can serve exceptionally well as an advanced under-
inclusionofnewchaptersinallsectionscoveredinthefirst graduateorgraduateleveltextforcellphysiologycourses.
edition.Thenewtopicsintroducedintothevarioussections The broad coverage of this second edition also makes it
include lipid structure, mitochondrial physiology, cell very attractive for use in cell biophysics, membrane
responses to hormones, red blood cell transport, neuron biology, and biomedical engineering courses. It can serve
physiology, developmental changes in ion channels, sono- equally well as a textbook for introductory courses in ion
transduction, excitation-contraction coupling, and electro- channelstructure and physiology.
plaxcells.Inaddition,thescopeoftheneweditionhasbeen I was pleased, and indeed proud, to be asked by my
valuably broadened by the inclusion of two entirely new colleague Nicholas Sperelakis to contribute the Foreword
sections. One titled Protozoa and Bacteria covers the to the second edition of the Cell Physiology Sourcebook.
physiologyoftheseorganismsintwochapters.Intheother, Thisbook clearly setsa new standard of excellence.
Cell Division and Programmed Cell Death, there are
chapters on the regulation ofcelldivision, the cancer cell, Thomas E. Thompson
apoptosis, and the effects of ionizing radiation. The 1997
xix
Foreword
Foreword to the Third Edition
When Nicholas Sperelakis kindly invited me to write this Unraveling the physicochemical mechanisms that nature
foreword, I wondered how I could possibly follow in the has discovered, fashioned, combined, and interwoven into
footsteps of Hugh Davson. I studied physiology at thetangledskeinofprocessesthatformthefunctionofeven
University College London (UCL) at the time when his thesimplestcellisaprocessfullofsurprisesaswediscover
monumental Textbook of General Physiology was pub- with awe the audacity with which nature’s molecular
lished. UCL was an extraordinary place in which to be mechanisms are reused again and again in different
astudentatthattime.NotonlywasHughDavsonlayinghis contexts. One might call this audacity the “dance of the
particular cornerstone of the subject, but Leonard Bayliss genes”wereitnotfortheinanimateandunthinkingnatureof
was also reworking his father’s famous Principles of thesebitsofcodethattransmitthelogicfromonegeneration
General Physiology. Thesewere the books that convinced to another. The logic is physiological, not genetic. The
me to become a research physiologist and that cell physi- molecularbiologistSydneyBrennerputthepointsuccinctly
ology was the place to begin. Between them, Davson and whenhewroterecently(inaNovartissymposiumtitledThe
Bayliss were responsible for seducing generations of Limits of Reductionism in Biology) that “Genes can only
medical students to discover the challenge and delights of specifythepropertiesoftheproteinstheycodefor,andany
physiologicalresearch.Later,asayounglectureratUCL,I integrativepropertiesofthesystemmustbe‘computed’by
rememberaskingHughDavsonwhyhedidn’tlecturevery their interactions.” We are approaching the point at which
much to the students. He simply replied: “Denis, I’ve ourunderstandingofthoseinteractionsisdeepenough for
written it all. Tell them to read!” Actually, that remark physiology to aspire to become the quantitative analytical
inspired me to reread his books. My copies are still in my discipline it needs to be to solve the problems it tackles.
library, andtheyarewell and trulythumbed. Brenner went on to remark, significantly, “This provides
It will be the greatest tribute to the work of Nicholas aframeworkforanalysisbysimulation.”Itisasignofthe
Sperelakis and his colleagues that the pages of their book maturity of our science that simulation is indeed also
willalsobecomethewell-thumbedbibleofanewgenera- becominganessentialtoolofanalysis.
tion of physiologists. They will be entering the discipline Itisfurthersuchasignthatthescopeofcellphysiology
atanexcitingtime,forcellphysiologyisthebaseonwhich isnowsowide.Thebreadthofthisbookisthereforeoneof
ourunderstandingofallaspectsofintegrativeandsystems its greatest strengths. The chapters encompass the great
physiology must rest. This book, therefore, will be an majorityofimportantmolecularandcellsystems,sothatit
essential source for all of us who aspire to understand the does indeed justify itstitleas asourcebook.
“logicoflife,”whichis,afterall,themeaningandoriginof
theword“physiology.”Lifehasnosingle“logic,”ofcourse. Denis Noble
xxi
