The rapidly inactivating potassium current (I_A) is important in controlling neuronal action potentials. Altered I_A function and K⁺ channel expression have been found in epilepsy, and activation of the transient receptor potential vanilloid 4 (TRPV4) channel is involved in epilepsy pathogenesis. This study examined whether TRPV4 affects Kv4.2 and K⁺ channel interacting protein (KCHIP) expression and I_A changes following pilocarpine-induced status epilepticus (PISE) in mice. Herein, hippocampal protein levels of Kv4.2 and KCHIP2 increased 3 h–3 d and decreased 7–30 d; that of KCHIP1 increased 3–24 h and decreased 3–30 d post-PISE. The TRPV4 antagonist HC-067047 attenuated the increased protein levels of Kv4.2 and KCHIP2 but not that of KCHIP1 post-PISE. The TRPV4 agonist GSK1016790A increased hippocampal protein levels of Kv4.2 and KCHIP2 but had no effect on KCHIP1 expression. HC-067047 attenuated the increased I_A in hippocampal pyramidal neurons 24 h and 3 d post-PISE. GSK1016790A increased I_A in hippocampal pyramidal neurons, shifting the voltage-dependent inactivation curve toward depolarization. The GSK1016790A-induced increase of I_A was blocked by protein kinase A and calcium/calmodulin-dependent kinase II antagonists but was unaffected by protein kinase C antagonists. We conclude that TRPV4 activation may be responsible for the increases of Kv4.2 and KCHIP2 expression in hippocampi and I_A in hippocampal pyramidal neurons in PISE mice, which are likely compensatory measures for hyperexcitability at the early stage of epilepsy.

中文翻译：

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TRPV4参与毛果芸香碱诱发小鼠癫痫持续状态早期快速失活钾通道的变化

快速失活的钾电流 ( I _A ) 在控制神经元动作电位方面很重要。在癫痫中发现了改变的I _A功能和K ^{+通道表达，并且瞬时受体电位香草酸4（TRPV4）通道的激活与癫痫发病机制有关。}本研究检查 TRPV4 是否影响 Kv4.2 和 K ⁺通道相互作用蛋白 (KCHIP) 表达和I _A毛果芸香碱诱导小鼠癫痫持续状态 (PISE) 后的变化。在此，Kv4.2 和 KCHIP2 的海马蛋白水平在 3 h-3 d 增加并在 7-30 d 减少；KCHIP1 在 PISE 后 3-24 小时增加并减少 3-30 天。TRPV4 拮抗剂 HC-067047 减弱了 PISE 后 Kv4.2 和 KCHIP2 增加的蛋白质水平，但不减弱 KCHIP1 的蛋白质水平。TRPV4 激动剂 GSK1016790A 增加 Kv4.2 和 KCHIP2 的海马蛋白水平，但对 KCHIP1 表达没有影响。HC-067047 在 PISE后 24 小时和 3 天减弱了海马锥体神经元中I _{A的增加。}GSK1016790A 增加海马锥体神经元中的I _A，使电压依赖性失活曲线向去极化方向移动。GSK1016790A 诱导的I增加_A被蛋白激酶 A 和钙/钙调蛋白依赖性激酶 II 拮抗剂阻断，但不受蛋白激酶 C 拮抗剂的影响。我们得出结论，TRPV4 激活可能是 PISE 小鼠海马中 Kv4.2 和 KCHIP2 表达增加和海马锥体神经元I _A表达增加的原因，这可能是癫痫早期过度兴奋的补偿措施。