In some central neurons, including cerebellar Purkinje neurons and subthalamic nucleus (STN) neurons, TTX-sensitive sodium channels show unusual gating behavior whereby some channels open transiently during recovery from inactivation. This “resurgent” sodium current is effectively activated immediately after action potential-like waveforms. Earlier work using Purkinje neurons suggested that the great majority of resurgent current originates from Nav1.6 sodium channels. Here we used a mouse mutant lacking Nav1.6 to explore the contribution of these channels to resurgent, transient, and persistent components of TTX-sensitive sodium current in STN neurons. The resurgent current of STN neurons from Nav1.6−/− mice was reduced by 63% relative to wild-type littermates, a less dramatic reduction than that observed in Purkinje neurons recorded under identical conditions. The transient and persistent currents of Nav1.6−/− STN neurons were reduced by ∼40 and 55%, respectively. The resurgent current present in Nav1.6−/− null STN neurons was similar in voltage dependence to that in wild-type STN and Purkinje neurons, differing only in having somewhat slower decay kinetics. These results show that sodium channels other than Nav1.6 can make resurgent sodium current much like that from Nav1.6 channels.
Sodium channels gone wild: resurgent current from neuronal and muscle channelopathies
