Wang Jeffrey Chi-Fei, Hsiao Hung-Tsung, Wu Sheng-Nan
Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Int J Mol Sci. 2025 Aug 31;26(17):8469. doi: 10.3390/ijms26178469.
QX-314 is a positively charged lidocaine derivative with the membrane-impermeant property. This compound applied at the intracellular side has been shown to suppress the voltage-gated Na current (), while lidocaine itself acts to suppress the hyperpolarization-activated cation current (). To what extent this drug may exert any effects on various plasmalemmal ionic currents still remains largely unknown. This investigation focused on the impact of QX-314 on ionic currents in GH cells derived from pituitary tumors. This compound applied extracellularly was noted to differentially suppress the amplitude of transient and late with an IC value of 93 and 42 μM, respectively. In GH cells dialyzed with QX-314 (10 μM), the amplitude evoked by a brief depolarizing step was decreased, and its inactivation was increased. Moreover, QX-314, when applied extracellularly at 100 μM, diminished the amplitude of the current with an IC of 68 μM. Intracellular dialysis with QX-314 also suppressed amplitude; moreover, the later application of oxaliplatin reversed this suppression. As cells were extracellularly and continually exposed to QX-314, the magnitude of the -mediated K current () was also effectively suppressed with an IC value of 73 μM. Furthermore, upon intracellular dialysis with QX-314 (10 μM), the degree of the voltage-dependent hysteresis (Hys) of during the long-lasting isosceles-triangular ramp voltage was decreased; during continued exposure to QX-314, further extracellular bath additions of PD118057 (10 μM) counteracted QX-314-induced suppression. However, the extracellular addition of QX-314 (100 μM) mildly suppressed the outward delayed rectifier K current in GH cells. Collectively, QX-314 effectively suppressed , , and in GH cells, a model of endocrine function, and these actions may contribute to their physiological functions, if similar effects are observed in vivo.
QX - 314是一种带正电荷的利多卡因衍生物，具有膜不通透性。已证明将该化合物应用于细胞内侧可抑制电压门控钠电流（），而利多卡因本身则作用于抑制超极化激活的阳离子电流（）。这种药物对各种质膜离子电流可能产生何种程度的影响在很大程度上仍不清楚。本研究聚焦于QX - 314对垂体肿瘤来源的GH细胞中离子电流的影响。注意到将该化合物应用于细胞外可分别以93和42 μM的IC值差异性地抑制瞬态和晚期的幅度。在用QX - 314（10 μM）透析的GH细胞中，短暂去极化步骤诱发的幅度降低，且其失活增加。此外，当以100 μM在细胞外应用QX - 314时，以68 μM的IC降低电流的幅度。用QX - 314进行细胞内透析也抑制了幅度；此外，随后应用奥沙利铂可逆转这种抑制。当细胞在细胞外持续暴露于QX - 314时，介导的钾电流（）的幅度也被有效抑制，IC值为73 μM。此外，在用QX - 314（10 μM）进行细胞内透析时，在持久的等腰三角形斜坡电压期间的电压依赖性滞后（Hys）程度降低；在持续暴露于QX - 314期间，进一步在细胞外浴中添加PD118057（10 μM）可抵消QX - 314诱导的抑制。然而，在细胞外添加QX - 314（100 μM）可轻度抑制GH细胞中的外向延迟整流钾电流。总体而言，QX - 314有效抑制了内分泌功能模型GH细胞中的、和，并且如果在体内观察到类似效应，这些作用可能有助于它们的生理功能。
