| First Author | Hund TJ | Year | 2010 |
| Journal | J Clin Invest | Volume | 120 |
| Issue | 10 | Pages | 3508-19 |
| PubMed ID | 20877009 | Mgi Jnum | J:165334 |
| Mgi Id | MGI:4837024 | Doi | 10.1172/JCI43621 |
| Citation | Hund TJ, et al. (2010) A beta(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest 120(10):3508-19 |
| abstractText | 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. |
