Location, location, regulation: a novel role for β-spectrin in the heart
Kevin J. Sampson, Robert S. Kass
Kevin J. Sampson, Robert S. Kass
Published September 27, 2010
Citation Information: J Clin Invest. 2010;120(10):3434-3437. https://doi.org/10.1172/JCI44810.
View: Text | PDF
Commentary

Location, location, regulation: a novel role for β-spectrin in the heart

Abstract

Voltage-gated Na+ channels (VGSCs) are responsible for the rising phase of the action potential in excitable cells, including neurons and skeletal and cardiac myocytes. Small alterations in gating properties can lead to severe changes in cellular excitability, as evidenced by the plethora of heritable conditions attributed to mutations in VGSCs highlighting the need to better understand VGSC regulation. In this issue of the JCI, Hund et al. identify the ability of a key structural protein, βIV-spectrin, to bind and recruit Ca2+/calmodulin kinase II to the channel at a cellular location key to successful action potential initiation and propagation, where it can mediate function and excitability.

Authors

Kevin J. Sampson, Robert S. Kass

×

Figure 2

The macromolecular complex associated with the VGSC Nav1.5 in cardiac myocytes.

Options: View larger image (or click on image) Download as PowerPoint
The macromolecular complex associated with the VGSC Nav1.5 in cardiac my...
(A) Ankyrin-G brings the VGSC in complex with the actin-spectrin cytoskeleton at the cardiac intercalated discs, where they can participate in initiation and propagation of the cardiac AP. (B) In this issue of the JCI, Hund et al. show that βIV-spectrin recruits CaMKIIδ to the Nav1.5-ankyrin complex and that CaMKIIδ then modulates function via phosphorylation of a serine in the I–II linker (19). Binding sites for a number of interacting proteins are also shown. CaM, calmodulin; FHF1B, fibroblast growth factor homologous factor 1B; Nedd4, Nedd4-like ubiquitin-protein ligases.