Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City 60002, Taiwan.
Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
Int J Mol Sci. 2022 Aug 26;23(17):9696. doi: 10.3390/ijms23179696.
Picaridin (icaridin), a member of the piperidine chemical family, is a broad-spectrum arthropod repellent. Its actions have been largely thought to be due to its interaction with odorant receptor proteins. However, to our knowledge, to what extent the presence of picaridin can modify the magnitude, gating, and/or the strength of voltage-dependent hysteresis (Hys) of plasmalemmal ionic currents, such as, voltage-gated Na current [], has not been entirely explored. In GH pituitary tumor cells, we demonstrated that with exposure to picaridin the transient () and late () components of voltage-gated Na current () were differentially stimulated with effective EC's of 32.7 and 2.8 μM, respectively. Upon cell exposure to it, the steady-state current versus voltage relationship was shifted to more hyperpolarized potentials. Moreover, its presence caused a rightward shift in the midpoint for the steady-state inactivate curve of the current. The cumulative inhibition of induced during repetitive stimuli became retarded during its exposure. The recovery time course from the block elicited, following the conditioning pulse stimulation, was satisfactorily fitted by two exponential processes. Moreover, the fast and slow time constants of recovery from the block by the same conditioning protocol were noticeably increased in the presence of picaridin. However, the fraction in fast or slow component of recovery time course was, respectively, increased or decreased with an increase in picaridin concentrations. The Hys's strength of persistent (), responding to triangular ramp voltage, was also enhanced during cell exposure to picaridin. The magnitude of resurgent () was raised in its presence. Picaritin-induced increases of or intrinsically in GH cells could be attenuated by further addition of ranolazine. The predictions of molecular docking also disclosed that there are possible interactions of the picaridin molecule with the hNa1.7 channel. Taken literally, the stimulation of exerted by the exposure to picaridin is expected to exert impacts on the functional activities residing in electrically excitable cells.
派卡瑞丁（icaridin），属于哌啶化学家族的一员，是一种广谱昆虫驱避剂。其作用机制很大程度上被认为是与气味受体蛋白相互作用的结果。然而，据我们所知，派卡瑞丁的存在在何种程度上可以改变质膜离子电流的幅度、门控和/或电压依赖性滞后（Hys）的强度，如电压门控钠电流[Na]，尚未完全被探索。在 GH 垂体肿瘤细胞中，我们证明了暴露于派卡瑞丁后，电压门控钠电流的瞬态（）和晚期（）成分分别受到有效 EC50 为 32.7 和 2.8 μM 的刺激。当细胞暴露于它时，稳态电流-电压关系[I-V]被转移到更超极化的电位。此外，它的存在导致电流稳态失活曲线的中点向右移动。在重复刺激期间，诱导的累积抑制在暴露于派卡瑞丁时变得延迟。在条件脉冲刺激后，从 阻断中恢复的时间过程可以通过两个指数过程令人满意地拟合。此外，在存在派卡瑞丁的情况下，通过相同的条件协议从 阻断中恢复的快和慢时间常数明显增加。然而，在派卡瑞丁浓度增加的情况下，恢复时间过程中快或慢成分的分数分别增加或减少。在暴露于派卡瑞丁期间，对三角斜坡电压响应的持久电流（）的滞后强度也增强。在其存在下，再生电流（）的幅度增加。在 GH 细胞中，派卡瑞丁诱导的 或 内在增加可以通过进一步添加雷诺嗪来减弱。分子对接的预测还揭示了派卡瑞丁分子与 hNa1.7 通道之间可能存在相互作用。从字面上讲，暴露于派卡瑞丁所产生的 刺激预计会对电兴奋细胞中的功能活动产生影响。
