Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice.
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 Na(v)1.6 sodium channels. Here we used a mouse mutant lacking Na(v)1.6 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 Na(v)1.6(-/-) 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 Na(v)1.6(-/-) STN neurons were reduced by approximately 40 and 55%, respectively. The resurgent current present in Na(v)1.6(-/-) 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 Na(v)1.6 can make resurgent sodium current much like that from Na(v)1.6 channels.
Do
Michael Tri H
MT
Dept. of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Bean
Bruce P
BP
D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D051379:Mice; D018345:Mice, Knockout; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D011689:Purkinje Cells / Q000502:physiology; D015222:Sodium Channels / Q000172:deficiency / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels