Na<SUP>+</SUP> channel regulation by Ca<SUP>2+</SUP>/calmodulin and Ca <SUP>2+</SUP>/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes
Aims Calmodulin (CaM) regulates Na+ channel gating through binding to an IQ-like motif in the C-terminus. Ca2+/CaM-dependent protein kinase II (CaMKII) regulates Ca2+ handling, and chronic overactivity of CaMKII is associated with left ventricular hypertrophy and dysfunction and lethal arrhythmias....
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| Autores principales: | , , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
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2010
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/104334 http://hdl.handle.net/11336/61762 |
| Aporte de: |
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I19-R120-10915-104334 |
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dspace |
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Universidad Nacional de La Plata |
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I-19 |
| repository_str |
R-120 |
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SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Ca2+/cam-dependent protein kinase ii Calcium Calmodulin Na-channel |
| spellingShingle |
Ciencias Médicas Ca2+/cam-dependent protein kinase ii Calcium Calmodulin Na-channel Aiba, Takeshi Hesketh, Geoffrey G. Liu, Ting Carlisle, Rachael Villa Abrille, María Celeste O'Rourke, Brian Akar, Fadi G. Tomaselli, Gordon F. Na<SUP>+</SUP> channel regulation by Ca<SUP>2+</SUP>/calmodulin and Ca <SUP>2+</SUP>/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes |
| topic_facet |
Ciencias Médicas Ca2+/cam-dependent protein kinase ii Calcium Calmodulin Na-channel |
| description |
Aims Calmodulin (CaM) regulates Na+ channel gating through binding to an IQ-like motif in the C-terminus. Ca2+/CaM-dependent protein kinase II (CaMKII) regulates Ca2+ handling, and chronic overactivity of CaMKII is associated with left ventricular hypertrophy and dysfunction and lethal arrhythmias. However, the acute effects of Ca 2+/CaM and CaMKII on cardiac Na+ channels are not fully understood.Methods and results Purified NaV1.5-glutathione-S-transferase fusion peptides were phosphorylated in vitro by CaMKII predominantly on the I-II linker. Whole-cell voltage-clamp was used to measure Na+ current (INa) in isolated guinea-pig ventricular myocytes in the absence or presence of CaM or CaMKII in the pipette solution. CaMKII shifted the voltage dependence of Na+ channel availability by ≈+5 mV, hastened recovery from inactivation, decreased entry into intermediate or slow inactivation, and increased persistent (late) current, but did not change INa decay. These CaMKII-induced changes of Na+ channel gating were completely abolished by a specific CaMKII inhibitor, autocamtide-2-related inhibitory peptide (AIP). Ca2+/CaM alone reproduced the CaMKII-induced changes of INa availability and the fraction of channels undergoing slow inactivation, but did not alter recovery from inactivation or the magnitude of the late current. Furthermore, the CaM-induced changes were also completely abolished by AIP. On the other hand, cAMP-dependent protein kinase A inhibitors did not abolish the CaM/CaMKII-induced alterations of INa function.Conclusion Ca 2+/CaM and CaMKII have distinct effects on the inactivation phenotype of cardiac Na+ channels. The differences are consistent with CaM-independent effects of CaMKII on cardiac Na+ channel gating. |
| format |
Articulo Articulo |
| author |
Aiba, Takeshi Hesketh, Geoffrey G. Liu, Ting Carlisle, Rachael Villa Abrille, María Celeste O'Rourke, Brian Akar, Fadi G. Tomaselli, Gordon F. |
| author_facet |
Aiba, Takeshi Hesketh, Geoffrey G. Liu, Ting Carlisle, Rachael Villa Abrille, María Celeste O'Rourke, Brian Akar, Fadi G. Tomaselli, Gordon F. |
| author_sort |
Aiba, Takeshi |
| title |
Na<SUP>+</SUP> channel regulation by Ca<SUP>2+</SUP>/calmodulin and Ca <SUP>2+</SUP>/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes |
| title_short |
Na<SUP>+</SUP> channel regulation by Ca<SUP>2+</SUP>/calmodulin and Ca <SUP>2+</SUP>/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes |
| title_full |
Na<SUP>+</SUP> channel regulation by Ca<SUP>2+</SUP>/calmodulin and Ca <SUP>2+</SUP>/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes |
| title_fullStr |
Na<SUP>+</SUP> channel regulation by Ca<SUP>2+</SUP>/calmodulin and Ca <SUP>2+</SUP>/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes |
| title_full_unstemmed |
Na<SUP>+</SUP> channel regulation by Ca<SUP>2+</SUP>/calmodulin and Ca <SUP>2+</SUP>/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes |
| title_sort |
na<sup>+</sup> channel regulation by ca<sup>2+</sup>/calmodulin and ca <sup>2+</sup>/calmodulin-dependent protein kinase ii in guinea-pig ventricular myocytes |
| publishDate |
2010 |
| url |
http://sedici.unlp.edu.ar/handle/10915/104334 http://hdl.handle.net/11336/61762 |
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Repositorios |
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