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Atrial arrhythmogenicity in aged Scn5a+/DeltaKPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction.

Guzadhur, L, Pearcey, SM, Duehmke, RM, Jeevaratnam, K, Hohmann, AF, Zhang, Y, Grace, AA, Lei, M and Huang, CL (2010) Atrial arrhythmogenicity in aged Scn5a+/DeltaKPQ mice modeling long QT type 3 syndrome and its relationship to Na+ channel expression and cardiac conduction. Pflugers Arch, 460 (3). pp. 593-601.

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Abstract

Recent studies have reported that human mutations in Nav1.5 predispose to early age onset atrial arrhythmia. The present experiments accordingly assess atrial arrhythmogenicity in aging Scn5a+/KPQ mice modeling long QT3 syndrome in relationship to cardiac Na(+) channel, Nav1.5, expression. Atrial electrophysiological properties in isolated Langendorff-perfused hearts from 3- and 12-month-old wild type (WT), and Scn5a+/KPQ mice were assessed using programmed electrical stimulation and their Nav1.5 expression assessed by Western blot. Cardiac conduction properties were assessed electrocardiographically in intact anesthetized animals. Monophasic action potential recordings demonstrated increased atrial arrhythmogenicity specifically in aged Scn5a+/DeltaKPQ hearts. These showed greater action potential duration/refractory period ratios but lower atrial Nav1.5 expression levels than aged WT mice. Atrial Nav1.5 levels were higher in young Scn5a+/DeltaKPQ than young WT. These levels increased with age in WT but not Scn5a+/DeltaKPQ. Both young and aged Scn5a+/DeltaKPQ mice showed lower heart rates and longer PR intervals than their WT counterparts. Young Scn5a+/DeltaKPQ mice showed longer QT and QTc intervals than young WT. Aged Scn5a+/DeltaKPQ showed longer QRS durations than aged WT. PR intervals were prolonged and QT intervals were shortened in young relative to aged WT. In contrast, ECG parameters were similar between young and aged Scn5a+/DeltaKPQ. Aged murine Scn5a+/DeltaKPQ hearts thus exhibit an increased atrial arrhythmogenicity. The differing Nav1.5 expression and electrocardiographic indicators of slowed cardiac conduction between Scn5a+/DeltaKPQ and WT, which show further variations associated with aging, may contribute toward atrial arrhythmia in aged Scn5a+/DeltaKPQ hearts.

Item Type: Article
Authors :
NameEmailORCID
Guzadhur, LUNSPECIFIEDUNSPECIFIED
Pearcey, SMUNSPECIFIEDUNSPECIFIED
Duehmke, RMUNSPECIFIEDUNSPECIFIED
Jeevaratnam, Kk.jeevaratnam@surrey.ac.ukUNSPECIFIED
Hohmann, AFUNSPECIFIEDUNSPECIFIED
Zhang, YUNSPECIFIEDUNSPECIFIED
Grace, AAUNSPECIFIEDUNSPECIFIED
Lei, MUNSPECIFIEDUNSPECIFIED
Huang, CLUNSPECIFIEDUNSPECIFIED
Date : August 2010
Identification Number : https://doi.org/10.1007/s00424-010-0851-z
Uncontrolled Keywords : Action Potentials, Aging, Animals, Atrial Fibrillation, Electrocardiography, Genotype, Heart Conduction System, Long QT Syndrome, Mice, Mutation, NAV1.5 Voltage-Gated Sodium Channel, Phenotype, Sodium Channels
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:27
Last Modified : 17 May 2017 14:49
URI: http://epubs.surrey.ac.uk/id/eprint/827848

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