Hallworth Nicholas E, Wilson Charles J, Bevan Mark D
University of Tennessee, Anatomy and Neurobiology, Memphis, Tennessee 38163, USA.
J Neurosci. 2003 Aug 20;23(20):7525-42. doi: 10.1523/JNEUROSCI.23-20-07525.2003.
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.
在帕金森病（PD）的正常自主运动和异常运动过程中，可观察到丘脑底核（STN）神经元有不同的活动模式。为了确定这种活动模式是如何由小电导钾（SK）/钙激活钾（KCa）通道和电压门控钙（Cav）通道调节的，采用穿孔膜片钳配置在脑片中记录STN神经元，[脑片取自出生后第16天（P16）至30天的大鼠，并保持在37℃]，然后用SK KCa通道拮抗剂蜂毒明肽或SK KCa通道激动剂1-乙基-2-苯并咪唑啉酮或Cav通道拮抗剂ω-芋螺毒素GVIA（Cav2.2选择性）或硝苯地平（Cav1.2-1.3选择性）[校正后]进行处理。在其他实验中，引入fura-2作为细胞内钙动力学的指标。单峰后超极化电流的一个成分对蜂毒明肽敏感，与通过Cav2.2通道的钙内流锁相，并且是精确、自主的单峰振荡所必需的。SK KCa/Cav2.2通道偶联并非动作电位频率适应的基础，但通过编码细胞内钙的积累来限制电流注入时的活动，维持特征性的S形频率-强度关系并产生串刺激后的超极化。此外，SK KCa通道在短持续时间爆发（<100毫秒）的神经元中比长持续时间爆发（>100毫秒）的神经元更有效地终止反弹爆发活动，推测是通过它们被Cav3通道激活。Cav1.2-1.3通道与SK KCa通道的偶联不强，因此支持二级范围和长持续时间的反弹爆发发放。总之SK KCa通道在STN神经元的自主、驱动和反弹活动中起基本作用，并对抗从自主、节律性单峰活动向爆发发放的转变。
