Tetraethylammonium chloride

Tetraethylammonium chloride is a non-specific potassium channel blocker whose main mechanism of action is to inhibit potassium ion efflux by binding to sites within the channel pores^[1]. Due to its positively charged quaternary ammonium structure, it is difficult to penetrate cell membranes and the blood-brain barrier, and therefore it is mainly used in in vitro electrophysiological experiments and cardiovascular research ^[2-3].

In canine tracheal smooth muscle cell, Tetraethylammonium chloride (15-30mM; 180min) significantly increased the efflux rates of ⁴²K and ⁸⁶Rb in normal Krebs solution ^[4]. In smooth muscle cells of the rabbit main pulmonary artery, Tetraethylammonium chloride (10-30mM; 30min) induced membrane depolarization, increased membrane resistance, generated anomalous rectification and occasional spike potentials in response to applied depolarizing current pulses, and produced sustained contractions ^[5]. In vascular smooth muscle cells, Tetraethylammonium chloride (10mM; 1h) elicited oscillatory contractions and enhanced intercellular communication among cultured cells ^[6].

In the isoflurane exposure model, Tetraethylammonium chloride (5mg/kg; ip; single administration) significantly inhibited caspase activity in the mouse anterior cerebral cortex and reduced necrotic cell death in the hippocampal region ^[7]. In conscious mouse experiments, Tetraethylammonium chloride (40mg/kg; po; single administration) enhanced intestinal propulsion of a charcoal suspension and significantly increased duodenal maximum contractile force, minimum relaxation force, and contraction amplitude ^[8].

References:
[1] Chand N, Diamantis W, Sofia R D. Induction of non-specific airway hyperreactivity by potassium channel blockade in rat isolated trachea[J]. British journal of pharmacology, 1990, 101(3): 541.
[2] Xia M, Shahane S A, Huang R, et al. Identification of quaternary ammonium compounds as potent inhibitors of hERG potassium channels[J]. Toxicology and applied pharmacology, 2011, 252(3): 250-258.
[3] Nand V, Doggrell S A. Effects of tetraethylammonium, 4‐aminopyridine and bretylium on cardiovascular tissues from normo‐and hypertensive rats[J]. Journal of pharmacy and pharmacology, 1999, 51(5): 631-640.
[4] Imaizumi Y, Watanabe M. The effect of tetraethylammonium chloride on potassium permeability in the smooth muscle cell membrane of canine trachea[J]. The Journal of Physiology, 1981, 316(1): 33-46.
[5] Haeusler G, Thorens S. Effects of tetraethylammonium chloride on contractile, membrane and cable properties of rabbit artery muscle[J]. The Journal of Physiology, 1980, 303(1): 203-224.
[6] Watts S W, Tsai M L, Loch-Caruso R, et al. Gap junctional communication and vascular smooth muscle reactivity: use of tetraethylammonium chloride[J]. Journal of vascular research, 1994, 31(5): 307-313.
[7] Jung S, Kayser E B, Johnson S C, et al. Tetraethylammonium chloride reduces anaesthetic-induced neurotoxicity in Caenorhabditis elegans and mice[J]. British Journal of Anaesthesia, 2022, 128(1): 77-88.
[8] Dong D L, Wang Q H, Chen W, et al. Contrasting effects of tetraethylammonium and 4-aminopyridine on the gastrointestinal function of mice[J]. European journal of pharmacology, 2005, 509(2-3): 179-185.

Tetraethylammonium chloride是一种非特异性钾通道阻滞剂，其主要作用机制是通过结合通道孔内部位点抑制钾离子外流 ^[1]。Tetraethylammonium chloride带正电荷的季铵结构，难以穿透细胞膜和血脑屏障，因此主要应用于体外电生理实验和心血管研究 ^[2-3]。

在犬气管平滑肌细胞中，Tetraethylammonium chloride（15-30mM；180min）显著增加了正常克氏液中⁴²K和⁸⁶Rb外流的速率 ^[4]。在家兔主肺动脉的平滑肌细胞中, Tetraethylammonium chloride（10-30mM；30min）使细胞膜去极化，增加膜电阻，对外加去极化电流脉冲产生异常整流和偶尔的尖峰电位，并产生持续收缩 ^[5]。在血管平滑肌细胞中，Tetraethylammonium chloride（10mM；1h） 诱导血管平滑肌的振荡收缩，并刺激培养细胞间的细胞通讯 ^[6]。

在异氟烷暴露模型中，Tetraethylammonium chloride (5mg/kg；ip；单次给药)抑制了小鼠大脑前皮层半胱天冬酶和海马体区域的坏死 ^[7]。Tetraethylammonium chloride（40mg/kg；po；单次给药）可增强清醒小鼠中炭末悬液的肠道推进，增加了十二指肠最大收缩力、最小松弛力和收缩振幅 ^[8]。