Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Eder, P; Probst, D; Rosker, C; Poteser, M; Wolinski, H; Kohlwein, SD; Romanin, C; Groschner, K.
Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex.
Cardiovasc Res. 2007; 73(1): 111-119.
Doi: 10.1016/j.cardiores.2006.10.016
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- Führende Autor*innen der Med Uni Graz
- Groschner Klaus
- Co-Autor*innen der Med Uni Graz
- Poteser Michael
- Rosker Christian
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- Abstract:
- Objective: Members of the classical transient receptor potential protein (TRPC) family are considered as key components of phospholipase C (PLC)-dependent Ca2+ signaling. Previous results obtained in the HEK 293 expression system suggested a physical and functional coupling of TRPC3 to the cardiac-type Na+/Ca2+ exchanger, NCX1 (sodium calcium exchanger 1). This study was designed to test for expression of TRPC3 (transient receptor potential channel 3) and for the existence of a native TRPC3/NCX1 signaling complex in rat cardiac myocytes. Methods: Protein expression and cellular distribution were determined by Western blot and immunocytochemistry. Protein-protein interactions were investigated by reciprocal co-immunoprecipitation and glutathione S-transferase (GST)-pulldown experiments. Recruitment of protein complexes into the plasma membrane was assayed by surface biotinylation. The functional role of TRPC3 was investigated by fluorimetric recording of angiotensin II-induced calcium signals employing a dominant negative knockdown strategy. Results: TRPC3 immunoreactivity was observed in surface plasma membrane regions and in an intracellular membrane system. Co-immunolabeling of TRPC3 and NCX1 indicated significant co-localization of the two proteins. Both co-immunoprecipitation and GST-pulldown experiments demonstrated association of TRPC3 with NCX1. PLC stimulation was found to trigger NCX-mediated Ca2+ entry, which was dependent on TRPC3-mediated Na+ loading of myocytes. This NCX-mediated Ca2+ signaling was significantly suppressed by expression of a dominant negative fragment of TRPC3. PLC stimulation was associated with increased membrane presentation of both TRPC3 and NCX1. Conclusion: These results suggest a PLC-dependent recruitment of a TPPC3-NCX1 complex into the plasma membrane as a pivotal mechanism for the control of cardiac Ca2+ homeostasis. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calcium - metabolism
- Cell Line -
- Cell Membrane - metabolism
- Cells, Cultured -
- Homeostasis -
- Humans -
- Immunohistochemistry - methods
- Immunoprecipitation - methods
- Microscopy, Confocal -
- Myocytes, Cardiac - chemistry Myocytes, Cardiac - metabolism
- Rats -
- Rats, Sprague-Dawley -
- Signal Transduction - physiology
- Sodium-Calcium Exchanger - metabolism
- TRPC Cation Channels - analysis TRPC Cation Channels - genetics TRPC Cation Channels - metabolism
- Transfection -
- Type C Phospholipases - metabolism
- Find related publications in this database (Keywords)
- transient receptor potential protein
- TRPC3
- Na/Ca-exchanger
- cardiac myocytes
- calcium signaling