Transient receptor potential V4 (TRPV4), a plasma membrane calcium channel, is implicated as a contributor to the initiation of chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel (PTX) is a commonly used anticancer drug that causes CIPN and lithium has been shown to prevent CIPN. However, the direct effect of PTX and lithium on TRPV4 is not clear. This study investigated these actions using biochemical, pharmacological, and electrophysiological approaches using a neuronal cell line (SH-SY5Y). The addition of pharmacologically appropriate levels of PTX increased the expression of TRPV4, TRPV4 currents, and TRPV4-dependent calcium fluxes. Prolonged exposure to PTX amplified the acute effects of TRPV4 expression, currents, and calcium fluxes. Pretreatment with lithium (1 mM) decreased TRPV4 currents and calcium fluxes in the absence and presence of PTX. These findings enhance our understanding of the properties and regulation of TRPV4, the cellular mechanisms of PTX-induced neuropathy, and the mechanism of lithium for prevention of CIPN.

瞬时受体电位 V4 (TRPV4) 是一种质膜钙通道，被认为是引发化疗引起的周围神经病变 (CIPN) 的一个因素。紫杉醇 (PTX) 是一种常用的抗癌药物，可引起 CIPN，锂已被证明可预防 CIPN。然而，PTX 和锂对 TRPV4 的直接影响尚不清楚。本研究使用神经元细胞系 (SH-SY5Y) 使用生化、药理学和电生理学方法研究了这些作用。添加药理学适当水平的 PTX 增加了 TRPV4、TRPV4 电流和 TRPV4 依赖性钙通量的表达。长期接触 PTX 会放大 TRPV4 表达、电流和钙通量的急性影响。在不存在和存在 PTX 的情况下，用锂 (1 mM) 预处理会降低 TRPV4 电流和钙通量。这些发现增强了我们对 TRPV4 的特性和调节、PTX 诱导的神经病变的细胞机制以及锂预防 CIPN 机制的理解。