Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice

Area of Science:

• Neuroscience
• Molecular Biology
• Electrophysiology

Background:

• TTX-sensitive sodium channels exhibit unique resurgent gating in central neurons like Purkinje and subthalamic nucleus (STN) neurons.
• This resurgent current activates post-action potential waveforms and was previously attributed mainly to Na(v)1.6 channels in Purkinje neurons.

Purpose of the Study:

• To investigate the contribution of Na(v)1.6 sodium channels to resurgent, transient, and persistent currents in STN neurons.
• To characterize the properties of resurgent sodium current in STN neurons lacking Na(v)1.6 channels.

Main Methods:

• Utilized a mouse mutant lacking Na(v)1.6 channels (Na(v)1.6(-/-)).
• Recorded TTX-sensitive sodium currents, including resurgent, transient, and persistent components, from STN neurons of Na(v)1.6(-/-) and wild-type littermates.
• Analyzed voltage dependence and decay kinetics of resurgent currents.

Main Results:

• Resurgent sodium current in STN neurons from Na(v)1.6(-/-) mice was reduced by 63% compared to wild-type.
• Transient and persistent currents were reduced by approximately 40% and 55%, respectively, in Na(v)1.6(-/-) STN neurons.
• Resurgent current in Na(v)1.6(-/-) STN neurons showed similar voltage dependence but slower decay kinetics compared to wild-type.

Conclusions:

• Na(v)1.6 channels contribute significantly but not exclusively to resurgent sodium current in STN neurons.
• Sodium channels other than Na(v)1.6 are capable of generating resurgent currents with properties similar to those mediated by Na(v)1.6.
• These findings highlight the diversity of sodium channel function in neuronal excitability and signaling.