Department of Cell Biology and Physiology, Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine , St. Louis, MO, USA.
J Gen Physiol. 2023 May 1;155(5). doi: 10.1085/jgp.202213273. Epub 2023 Mar 13.
The Vanilloid thermoTRP (TRPV1-4) subfamily of TRP channels are involved in thermoregulation, osmoregulation, itch and pain perception, (neuro)inflammation and immune response, and tight control of channel activity is required for perception of noxious stimuli and pain. Here we report voltage-dependent modulation of each of human TRPV1, 3, and 4 by the endogenous intracellular polyamine spermine. As in inward rectifier K channels, currents are blocked in a strongly voltage-dependent manner, but, as in cyclic nucleotide-gated channels, the blockade is substantially reduced at more positive voltages, with maximal blockade in the vicinity of zero voltage. A kinetic model of inhibition suggests two independent spermine binding sites with different affinities as well as different degrees of polyamine permeability in TRPV1, 3, and 4. Given that block and relief occur over the physiological voltage range of action potentials, voltage-dependent polyamine block may be a potent modulator of TRPV-dependent excitability in multiple cell types.
香草素瞬时受体电位 (TRPV) 通道的类香草酸热感受器 (TRPV1-4) 亚家族参与体温调节、渗透压调节、瘙痒和疼痛感知、（神经）炎症和免疫反应，并且需要对通道活性进行严格控制，以感知有害刺激和疼痛。在这里，我们报告了内源性细胞内多胺亚精胺对人 TRPV1、3 和 4 的电压依赖性调制。与内向整流钾通道一样，电流以强烈的电压依赖性方式被阻断，但是，与环核苷酸门控通道一样，在更正的电压下，阻断作用会大大降低，在接近零电压的情况下，阻断作用最大。抑制的动力学模型表明 TRPV1、3 和 4 中存在两个具有不同亲和力以及不同多胺通透性的独立亚精胺结合位点。鉴于阻断和缓解发生在动作电位的生理电压范围内，电压依赖性多胺阻断可能是多种细胞类型中 TRPV 依赖性兴奋性的有效调节剂。
