Excitability of paraventricular nucleus neurones that project to the rostral ventrolateral medulla is regulated by small-conductance Ca2+-activated K+ channels
Excitability of paraventricular nucleus neurones that project to the rostral ventrolateral medulla is regulated by small-conductance Ca2+-activated K+ channels
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DOI：
10.1113/jphysiol.2009.175364
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发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Toney, Glenn M.
中科院分区：
文献类型：
--
作者：
Chen, Qing-Hui;Toney, Glenn M.
采用全细胞膜片钳技术研究大鼠室旁核（PVN）直接投射到延髓头端腹外侧区（RVLM）神经元（PVN-RVLM神经元）兴奋性的调节机制。在电压钳记录中，阶跃去极化引起钙依赖性外向尾电流，在E-K附近逆转。该电流几乎被apamin和UCL 1684消除，表明通过小电导Ca 2+激活的K+（SK）通道进行调解。在电流钳记录中，去极化阶跃电流注入诱发了经历尖峰频率适应（SFA）的动作电位。用apamin或UCL 1684阻断SK通道增加了尖峰频率，而不改变SFA的速率。终止阶跃电流注入后，观察到一个突出的中等后超极化电位（mAHP）。SK通道阻断取消了mAHP，并揭示了后去极化电位（ADP）。响应于斜坡电流注入，在SK通道阻断期间亚阈值去极化的速率增加，表明去极化输入电阻增加。微型EPSC的频率，幅度和衰减动力学未改变浴应用apamin，这表明SK通道阻滞可能增加兴奋性的突触后作用。我们的结论是，虽然SK通道在PVN-RVLM神经元中产生SFA的作用不大，但它们的激活确实抑制了兴奋性。该机制似乎涉及激活一个mAHP，反对一个突出的ADP，否则将促进射击。
Whole cell patch-clamp recordings were performed in brain slices to investigate mechanisms regulating the excitability of paraventricular nucleus (PVN) neurones that project directly to the rostral ventrolateral medulla (RVLM) (PVN-RVLM neurones) of rats. In voltage-clamp recordings, step depolarization elicited a calcium-dependent outward tail current that reversed near E-K. The current was nearly abolished by apamin and by UCL1684, suggesting mediation by small-conductance Ca2+-activated K+ (SK) channels. In current-clamp recordings, depolarizing step current injections evoked action potentials that underwent spike-frequency adaptation (SFA). SK channel blockade with apamin or UCL1684 increased the spike frequency without changing the rate of SFA. Upon termination of step current injection, a prominent medium after-hyperpolarization potential (mAHP) was observed. SK channel blockade abolished the mAHP and revealed an after-depolarization potential (ADP). In response to ramp current injections, the rate of sub-threshold depolarization was increased during SK channel blockade, indicating that depolarizing input resistance was increased. Miniature EPSC frequency, amplitude, and decay kinetics were unaltered by bath application of apamin, suggesting that SK channel blockade likely increased excitability by a postsynaptic action. We conclude that although SK channels play little role in generating SFA in PVN-RVLM neurones, their activation nevertheless does dampen excitability. The mechanism appears to involve activation of a mAHP that opposes a prominent ADP that would otherwise facilitate firing.