| First Author | Kakizawa S | Year | 2007 |
| Journal | EMBO J | Volume | 26 |
| Issue | 7 | Pages | 1924-33 |
| PubMed ID | 17347645 | Mgi Jnum | J:122513 |
| Mgi Id | MGI:3714568 | Doi | 10.1038/sj.emboj.7601639 |
| Citation | Kakizawa S, et al. (2007) Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. EMBO J 26(7):1924-33 |
| abstractText | Functional crosstalk between cell-surface and intracellular ion channels plays important roles in excitable cells and is structurally supported by junctophilins (JPs) in muscle cells. Here, we report a novel form of channel crosstalk in cerebellar Purkinje cells (PCs). The generation of slow afterhyperpolarization (sAHP) following complex spikes in PCs required ryanodine receptor (RyR)-mediated Ca(2+)-induced Ca(2+) release and the subsequent opening of small-conductance Ca(2+)-activated K(+) (SK) channels in somatodendritic regions. Despite the normal expression levels of these channels, sAHP was abolished in PCs from mutant mice lacking neural JP subtypes (JP-DKO), and this defect was restored by exogenously expressing JPs or enhancing SK channel activation. The stimulation paradigm for inducing long-term depression (LTD) at parallel fiber-PC synapses adversely established long-term potentiation in the JP-DKO cerebellum, primarily due to the sAHP deficiency. Furthermore, JP-DKO mice exhibited impairments of motor coordination and learning, although normal cerebellar histology was retained. Therefore, JPs support the Ca(2+)-mediated communication between voltage-gated Ca(2+) channels, RyRs and SK channels, which modulates the excitability of PCs and is fundamental to cerebellar LTD and motor functions. |
