Who needs A current? Functional remodelling in the Kv4.2-I-mouse

摘要

Potassium channels are key sculptors of neuronal excitability. In contrast to the wealth of knowledge about these channels in expression systems, it has proven exceedingly difficult to pinpoint the actions of specific subunits in native membranes. This is due to inadequate pharmacological tools, as well as expression of many alpha subunits in individual cells, heteromul-timeric channels, auxiliary subunits, and overlap in channel biophysical properties. It is widely accepted that genetic manipulations are ultimately required to unravel this knot, but this approach has its own limitations. One concern is the potential compensation for loss of one subunit by altered expression of existing subunits or de novo expression of novel subunits. In this issue of The Journal of Physiology, Nerbonne and colleagues (Nerbonne etal. 2008) provide a compelling example of functional compensation after knock out of the Kv4.2 alpha subunit in visual cortical pyramidal neurons.