科研之友
微信
新浪微博
Facebook
分享链接
摘要
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.
- 出版日期2010-10
