Apamin-sensitive small conductance calcium-activated potassium channels, through their selective coupling to voltage-gated calcium channels, are critical determinants of the precision, pace, and pattern of action potential generation in rat subthalamic nucleus neurons in vitro.
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 potassium (SK)/calcium-activated potassium (KCa) channels 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 degrees C] and then treated with the SK KCa channel antagonist apamin or the SK KCa channel agonist 1-ethyl-2-benzimidazolinone or the Cav channel antagonists w-omega-conotoxin GVIA (Cav2.2-selective) or nifedipine (Cav1.2-1.3-selective) [corrected]. 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/Cav2.2 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 a post-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. Cav1.2-1.3 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.
Hallworth
Nicholas E
NE
University of Tennessee, Anatomy and Neurobiology, Memphis, Tennessee 38163, USA.
Wilson
Charles J
CJ
Bevan
Mark D
MD
D000200:Action Potentials; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D017136:Ion Transport; D007700:Kinetics; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels; D020531:Subthalamic Nucleus / Q000166:cytology / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D002118:Calcium