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

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, β(IV)-spectrin, to bind and recruit Ca(2+)/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.