Distinct activity patterns in subthalamic nucleus (STN) neurons are observed during normal voluntary movement and abnormal movement in Parkinson's disease (PD). To determine how such patterns of activity are regulated by small conductance (SK) calcium-activated potassium channels (KCa) and voltage-gated calcium (Cav) channels, STN neurons were recorded in the perforated patch configuration in slices, [which were prepared from postnatal day 16 (P16)-P30 rats and held at 37°C] and then treated with the SK KCa channel antagonist apamin or the SK KCa agonist 1-ethyl-2-benzimidazolinone or the Cav channel antagonists ω-conotoxin GVIA (Cav2.2-selective) or nifedipine (Ca v1.2-1.3-selective). In other experiments, fura-2 was introduced as an indicator of intracellular calcium dynamics. A component of the current underlying single-spike afterhyperpolarization was sensitive to apamin, phase-locked to calcium entry via Cav2.2 channels, and necessary for precise, autonomous, single-spike oscillation. SK KCa/Ca v2.2 channel coupling did not underlie spike-frequency adaptation but limited activity in response to current injection by encoding the accumulation of intracellular calcium, maintained the characteristic sigmoidal frequency-intensity relationship and generated apost-train afterhyperpolarization. In addition, SK KCa channels terminated rebound burst activity more effectively in neurons with short-duration bursts (< 100 msec) than neurons with long-duration bursts (> 100 msec), presumably through their activation by Cav3 channels. Ca v1.2-1.3 channels were not strongly coupled to SK KCa channels and therefore supported secondary range and long-duration rebound burst firing. In summary, SK KCa channels play a fundamental role in autonomous, driven, and rebound activity and oppose the transition from autonomous, rhythmic, single-spike activity to burst firing in STN neurons.
|Original language||English (US)|
|Number of pages||18|
|Journal||Journal of Neuroscience|
|State||Published - Aug 20 2003|
- Basal ganglia
- Rebound burst
ASJC Scopus subject areas