Abstract 1082: Cytoskeletal Protein 4.1R Affects Repolarisation And Regulates Calcium Handling In The Heart

Autor: Gopal K. Soppa, Nadia Sohrabi, Joon Lee, Magdi H. Yacoub, Jennifer C. Pinder, Cesare M. Terracciano, Mark A. Stagg, Urszula Siedlecka, Paul J.R. Barton, Pauline M. Bennett
Rok vydání: 2007
Předmět:
Zdroj: Circulation. 116
ISSN: 1524-4539
0009-7322
DOI: 10.1161/circ.116.suppl_16.ii_216-c
Popis: The 4.1 proteins are a family of multifunctional adaptor proteins that organise signalling/transport/cell adhesion molecules. They are capable of interaction with the spectrin-actin network thereby conferring mechanical stability to the cell membrane, with several ion transporters associated to this macromolecular complex. Protein 4.1R is expressed in the heart and upregulated in deteriorating human heart failure. However, no data exists on the roles of protein 4.1R in myocardial regulation and function. In particular, it is unknown whether this protein can influence cardiac contractility and/or electrophysiology. 4.1R-deficient mice (KO) were studied using echocardiography and ECG monitoring with radiotelemetry. Left ventricular dimensions were increased in KO mice (LV diameter - Dia (cm): WT = 0.43 ± 0.01 [6] (mean ± SEM [n]); KO = 0.49 ± 0.01 [6]; p < 0.01) - Sys cm): WT = 0.29 ± 0.01 [6]; KO = 0.34 ± 0.02 [6]; p < 0.05) with no changes in ejection fraction and fractional shortening. ECG analysis revealed reduced heart rate (RR interval (ms): WT = 113±5 [6]; KO = 139 ± 601 [6]; p < 0.01) accompanied by prolonged QT interval (corrected (ms): WT = 46 ± 2 [6]; KO = 52 ± 1 [6]; p < 0.05). The action potential duration (APD) measured in isolated ventricular myocytes was prolonged in KO (APD 90% at 1Hz (ms) WT = 146 ± 20 [21]; KO = 231 ± 29 [28]; p < 0.05). Ca transients, elicited by 1Hz field-stimulation and measured using the fluorescent indicator indo-1, were larger (amplitude (ratio units r.u.): WT = 0.07 ± 0.006 [22]; KO = 0.1 ± 0.006 [33]; p
Databáze: OpenAIRE
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