Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation

Neurons of the subthalamic nucleus (STN) are spontaneously active. By voltage clamping dissociated rat STN neurons with their own firing patterns, we found that pacemaking is driven by two kinds of subthreshold sodium current: a steady-state "persistent" sodium current and a dynamic "resurgent" sodium current, which promotes rapid firing by flowing immediately after a spike. These currents are strongly regulated by a process of slow inactivation that is active at physiological firing frequencies. Slow inactivation of the pacemaking sodium currents promotes a constant frequency of tonic firing in the face of small, steady changes in input and constitutes a form of adaptation at the single-cell level. Driving cells at a high rate (75 Hz) produced pronounced slow inactivation (60%-70%) of resurgent, persistent, and transient components of sodium current. This inactivation is likely to contribute to effects of clinical deep-brain stimulation on STN excitability.