Analysis of potassium channel functions in mammalian axons by gene knockouts

Mammalian axons express a rich repertoire of various K channel subtypes whose distribution is profoundly affected by myelination. In the past two decades, functional analysis of axonal K channels has been approached primarily through pharmacology. Recently, gene knockout techniques have been used to specifically delete a particular K channel subtype from axons. This is significant since the bulk of K channels in a myelinated nerve are covered by the myelin, making functional analysis of specific K channel subtypes by traditional means difficult. This review summarizes the first mutational analysis of this sort performed on an axonal fast K channel termed Kv1.1. This K channel is concealed by the myelin loops in the paranodes of all major myelinated fiber tracts, and exhibits highly heterogeneous distribution even in certain non-myelinated CNS axons. Physiological analysis of Kv1.1 null mutants suggest novel functions for this axonal K channel subtype, including modulation of conduction failures at branch points and stabilization of transition zones in myelinated nerves.