Abstract
Abstract 237: Transient Activation of Pkc Results in Long-lasting Detrimental Effects on Systolic [ca 2+ ] I in Cardiomyocytes by Altering Actin Cytoskeletal Dynamics and T-tubule Integrity
Circulation research, Vol.119(suppl_1)
07/22/2016
DOI: 10.1161/res.119.suppl_1.237
Abstract
Protein kinase C (PKC) family isozymes contribute to the development of heart failure through dysregulation of Ca
2+
handling properties and disruption of contractile function in cardiomyocytes. However, the majority of studies have examined either the acute or chronic effects of PKC activation or inhibition, yet PKC is likely only transiently activated under pathological conditions. Herein, we report that transient activation of PKC in cultured cardiomyocytes promotes long-term deleterious effects on the integrity of the transverse (T)- tubule system, resulting in a significant decrease in the amplitude and increase in the rising kinetics of Ca
2+
transients. Treatment with a PKCα/β inhibitor restored the synchronization of Ca
2+
transients and maintained T-tubule integrity in cultured cardiomyocytes. Studies using a dominant negative PKCα identified PKCα as the mediator of T-tubule remodeling in cardiomyocytes. Supporting these data, PKCα/β inhibition protected against T-tubule remodeling and cardiac dysfunction in a mouse model of pressure overload-induced heart failure. Mechanistically, transient activation of PKC resulted in biphasic actin cytoskeletal rearrangement. Transient inhibition of actin polymerization or depolymerization resulted in severe T-tubule damage, recapitulating the T-tubule damage induced by PKC activation. Moreover, inhibition of stretch activated channels (SAC) protected against T-tubule remodeling and E-C coupling dysfunction induced by transient PKC activation and actin cytoskeletal rearrangement. These data identify a key mechanistic link between transient PKC activation and long-term Ca
2+
handling defects through PKC-induced actin cytoskeletal rearrangement and resultant T-tubule damage.
Details
- Title: Subtitle
- Abstract 237: Transient Activation of Pkc Results in Long-lasting Detrimental Effects on Systolic [ca 2+ ] I in Cardiomyocytes by Altering Actin Cytoskeletal Dynamics and T-tubule Integrity
- Creators
- Ang Guo - University of IowaLong-Sheng Song - University of IowaBiyi Chen - University of IowaRong Chen - Shanghai Jiao Tong UniversityChunkai Huang - Shanghai Jiao Tong UniversityYihui Wang - Shanghai Jiao Tong University
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.119(suppl_1)
- DOI
- 10.1161/res.119.suppl_1.237
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 07/22/2016
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Biochemistry and Molecular Biology
- Record Identifier
- 9984297460302771
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