Membrane lipids are key determinants in the regulation of voltage-gated ion channels. Phosphatidylinositol 4,5-bisphosphate (PIP₂), a native membrane phospholipid, has been involved in the maintenance of the current amplitude and in the voltage-independent regulation of voltage-gated calcium channels (VGCC). However, the nature of the PIP₂ regulation on VGCC has not been fully elucidated. This work aimed to investigate whether the interacting PIP₂ electrostatic charges may account for maintaining the current amplitude of Ca_V2.2 channels. Furthermore, we tested whether charge shielding of PIP₂ mimics the voltage-independent inhibition induced by M₁ muscarinic acetylcholine receptor (M₁R) activation. Therefore, neomycin, a polycation that has been shown to block electrostatic interactions of PIP_2, was intracellularly dialyzed in superior cervical ganglion (SCG) neurons of the rat. Consistently, neomycin time-dependently diminished the calcium current amplitude letting the channel exhibit the hallmarks of the voltage-independent regulation. These results support that interacting PIP₂ charges not only underly the maintenance of the channel-current but also that charge screening of PIP₂ by itself unveils the voltage-independent features of Ca_V2.2 channels in SCG neurons.

膜脂质是调节电压门控离子通道的关键决定因素。磷脂酰肌醇4,5-二磷酸酯（PIP ₂），一种天然的膜磷脂，已参与维持电流振幅和电压门控钙通道（VGCC）的电压非独立调节。但是，关于VGCC的PIP ₂法规的性质尚未完全阐明。这项工作旨在调查相互作用的PIP ₂静电荷是否可以解释维持Ca _V 2.2通道的电流幅度。此外，我们测试了PIP _2的电荷屏蔽是否模仿了M ₁诱导的电压独立抑制毒蕈碱乙酰胆碱受体（M ₁ R）激活。因此，新霉素（一种已经显示出可以阻止PIP ₂静电相互作用的聚阳离子）在大鼠的上颈神经节（SCG）神经元中进行了细胞内透析。始终如一的是，新霉素在时间上减少了钙电流幅度，使通道表现出了电压依赖性调节的标志。这些结果表明，相互作用的PIP ₂不仅会在根本上维持通道电流的电荷，而且本身对PIP ₂的电荷筛选也揭示了SCG神经元中Ca _V 2.2通道的电压独立特征。