Table Of ContentHandbook of
Experimental Pharmacology
Volume 171
Editor-in-Chief
K.Starke,Freiburgi.Br.
EditorialBoard
G.V.R.Born,London
M.Eichelbaum,Stuttgart
D.Ganten,Berlin
F.Hofmann,München
W.Rosenthal,Berlin
G.Rubanyi,Richmond,CA
Basis and Treatment
of Cardiac Arrhythmias
Contributors
M.E.Anderson,C.Antzelevitch,J.R.Balser,P.Bennett,
M.Cerrone,C.E.Clancy,I.S.Cohen,J.M.Fish,I.W.Glaaser,
T.J.Hund,M.J.Janse,C.January,R.S.Kass,J.Kurokawa,
J.Lederer,S.O.Marx,A.J.Moss,S.Nattel,C.Napolitano,
S.Priori,G.Robertson,R.B.Robinson,D.M.Roden,
M.R.Rosen,Y.Rudy,A.Shiroshita-Takeshita,K.Sipido,
Y.Tsuji,P.C.Viswanathan,X.H.T.Wehrens,S.Zicha
Editors
Robert S. Kass and Colleen E. Clancy
123
RobertS.KassPh.D.
DavidHosackProfessorandChairman
ColumbiaUniversity
DepartmentofPharmacology
630W.168St.
NewYork,NY10032
USA
e-mail:[email protected]
ColleenE.ClancyPh.D.
AssistantProfessor
DepartmentofPhysiologyandBiophysics
InstituteforComputationalBiomedicine
WeillMedicalCollegeofCornellUniversity
1300YorkAvenue
LC-501E
NewYork,NY10021
e-mail:[email protected]
With60Figuresand11Tables
ISSN 0171-2004
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Preface
In thepastdecade,major progresshasbeenmadeinunderstandingmecha-
nismsofarrhythmias.Thisprogressstemsfrommuch-improvedexperimen-
tal,genetic,andcomputationaltechniquesthathavehelpedtoclarifytheroles
of specific proteins in the cardiac cycle, including ion channels, pumps, ex-
changer,adaptorproteins,cell-surfacereceptors,andcontractileproteins.The
interactionsofthesecomponents,andtheirindividualpotentialastherapeu-
tictargets,havealsobeenstudiedindetail,viaanarrayofnewimagingand
sophisticatedexperimentalmodalities.Thepast10yearshavealsoledtothe
realizationthatgeneticsplaysapredominantroleinthedevelopmentoflethal
arrhythmias.
Many of the topics discussed in this text reflect very recently undertaken
researchdirectionsincludingthegeneticsofarrhythmias,cellsignalingmole-
culesaspotentialtherapeutictargets,andtraffickingtothemembrane.These
newapproachesandimplementationsofanti-arrhythmictherapyderivefrom
manydecadesofresearchasoutlinedinthefirstchapterbythedistinguished
professorsMichaelRosen(ColumbiaUniversity)andMichielJanse(University
ofAmsterdam).Thetextcoverschangesinapproachestoarrhythmiatherapy
over time, in multiple cardiac regions, and over many scales, from gene to
proteintocelltotissuetoorgan.
NewYork,May2005 ColleenE.ClancyandRobertS.Kass
ListofContents
HistoryofArrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . 1
M.J.Janse,M.R.Rosen
PacemakerCurrentandAutomaticRhythms:
TowardaMolecularUnderstanding . . . . . . . . . . . . . . . . . . . . 41
I.S.Cohen,R.B.Robinson
Proarrhythmia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
D.M.Roden,M.E.Anderson
CardiacNa+ChannelsasTherapeuticTargets
forAntiarrhythmicAgents . . . . . . . . . . . . . . . . . . . . . . . . . 99
I.W.Glaaser,C.E.Clancy
StructuralDeterminantsofPotassiumChannelBlockade
andDrug-InducedArrhythmias . . . . . . . . . . . . . . . . . . . . . . 123
X.H.T.Wehrens
SodiumCalciumExchangeasaTargetforAntiarrhythmicTherapy . . . 159
K.R.Sipido,A.Varro,D.Eisner
ARoleforCalcium/Calmodulin-DependentProteinKinaseII
inCardiacDiseaseandArrhythmia . . . . . . . . . . . . . . . . . . . . 201
T.J.Hund,Y.Rudy
AKAPsasAntiarrhythmicTargets? . . . . . . . . . . . . . . . . . . . . 221
S.O.Marx,J.Kurokawa
β
-BlockersasAntiarrhythmicAgents . . . . . . . . . . . . . . . . . . . 235
S.Zicha,Y.Tsuji,A.Shiroshita-Takeshita,S.Nattel
ExperimentalTherapyofGeneticArrhythmias:
Disease-SpecificPharmacology . . . . . . . . . . . . . . . . . . . . . . 267
S.G.Priori,C.Napolitano,M.Cerrone
Mutation-SpecificPharmacologyoftheLongQTSyndrome . . . . . . . 287
R.S.Kass,A.J.Moss
VIII ListofContents
TherapyfortheBrugadaSyndrome . . . . . . . . . . . . . . . . . . . . 305
C.Antzelevitch,J.M.Fish
MolecularBasisofIsolatedCardiacConductionDisease . . . . . . . . . 331
P.C.Viswanathan,J.R.Balser
hERGTraffickingandPharmacologicalRescue
ofLQTS-2MutantChannels . . . . . . . . . . . . . . . . . . . . . . . . 349
G.A.Robertson,C.T.January
SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
ListofContributors
(Addressesstatedatthebeginningofrespectivechapters)
Anderson,M.E. 73 Moss,A.J. 287
Antzelevitch,C. 305
Napolitano,C. 267
Balser,J.R. 331 Nattel,S. 235
Cerrone,M. 267 Priori,S.G. 267
Clancy,C.E. 99
Cohen,I.S. 41 Robertson,G.A. 349
Robinson,R.B. 41
Eisner,D. 159 Roden,D.M. 73
Rosen,M.R. 1
Fish,J.M. 305 Rudy,Y. 201
Glaaser,I.W. 99 Shiroshita-Takeshita,A. 235
Sipido,K.R. 159
Hund,T.J. 201
Tsuji,Y. 235
Janse,M.J. 1
January,C.T. 349 Varro,A. 159
Viswanathan,P.C. 331
Kass,R.S. 287
Kurokawa,J. 221 Wehrens,X.H.T. 123
Marx,S.O. 221 Zicha,S. 235
