Journal article
A beta(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice
The Journal of clinical investigation, Vol.120(10), pp.3508-3519
10/01/2010
DOI: 10.1172/JCI43621
PMCID: PMC2947241
PMID: 20877009
Abstract
Ion channel function is fundamental to the existence of Life. In metazoans, the coordinate activities of voltage-gated Na+ channels underlie cellular excitability and control neuronal communication, cardiac excitation-contraction coupling, and skeletal muscle function. However, despite decades of research and linkage of Na+ channel dysfunction with arrhythmia, epilepsy, and myotonia, little progress has been made toward understanding the fundamental processes that regulate this family of proteins. Here, we have identified beta(IV)-spectrin as a multifunctional regulatory platform for Na+ channels in mice. We found that beta(IV)-spectrin targeted critical structural and regulatory proteins to excitable membranes in the heart and brain. Animal models harboring mutant beta(IV)-spectrin alleles displayed aberrant cellular excitability and whole animal physiology. Moreover, we identified a regulatory mechanism for Na+ channels, via direct phosphorylation by beta(IV)-spectrin-targeted calcium/calmodulin-dependent kinase II (CaMKII). Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain.
Details
- Title: Subtitle
- A beta(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice
- Creators
- Thomas J. Hund - University of IowaOlha M. Koval - University of IowaJingdong Li - University of IowaPatrick J. Wright - University of IowaLan Dian - Univ Iowa, Carver Coll Med, Dept Internal Med, Div Cardiovasc Med, Iowa City, IA 52242 USAJedidiah S. Snyder - University of IowaHjalti Gudmundsson - University of IowaCrystal F. Kline - University of IowaNathan P. Davidson - University of IowaNatalia Cardona - University of IowaMatthew N. Rasband - Baylor College of MedicineMark E. Anderson - University of IowaPeter J. Mohler - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.120(10), pp.3508-3519
- Publisher
- Amer Soc Clinical Investigation Inc
- DOI
- 10.1172/JCI43621
- PMID
- 20877009
- PMCID
- PMC2947241
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Number of pages
- 12
- Grant note
- Pew Scholars Trust Fondation Leducq Award R01HL084583 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) UL1RR024979 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) HL084583; HL083422; HL079031; HL62494; HL70250; NS044916; HL096805 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R37NS044916 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Language
- English
- Date published
- 10/01/2010
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359934402771
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