Jonsson Malin, Dabrowski Michael, Gurley David A, Larsson Olof, Johnson Edwin C, Fredholm Bertil B, Eriksson Lars I
Department of Anesthesiology and Intensive Care Medicine, Karolinska University Hospital and Karolinska Institutet, Sweden.
Anesthesiology. 2006 Apr;104(4):724-33. doi: 10.1097/00000542-200604000-00017.
Succinylcholine is one of the most widely used muscle relaxants in clinical anesthesia and emergency medicine. Although the clinical advantages and cardiovascular side effects are well known, its mechanism of action within the human nicotinic cholinergic receptor system remains to be understood. The aim of this study was to investigate the effect of succinylcholine on human muscle and neuronal nicotinic acetylcholine receptor (nAChR) subtypes.
Xenopus laevis oocytes were injected with human messenger RNA for muscle and neuronal nAChR subunits. Receptor activation, desensitization, and inhibition induced by the natural ligand acetylcholine or by succinylcholine was studied using a multichannel two-electrode voltage clamp setup. Responses were measured as peak current and net charge.
Succinylcholine concentration-dependently activated the muscle-type nAChR with an EC50 value of 10.8 microm (95% confidence interval, 9.8-11.9 microm), and after the initial activation, succinylcholine desensitized the muscle-type nAChR. Succinylcholine did not activate the neuronal nAChR subtypes alpha3beta2, alpha3beta4, alpha4beta2, or alpha7 at concentrations up to 1 mm and was a poor inhibitor at these receptor subtypes, with IC50 values above 100 microm.
Succinylcholine activates the muscle-type nAChR followed by desensitization. The observation that succinylcholine does not inhibit the presynaptic alpha3beta2 autoreceptor at clinically relevant concentrations provides a possible mechanistic explanation for the typical lack of tetanic fade in succinylcholine-induced neuromuscular blockade. Finally, cardiovascular side effects (e.g., tachyarrhythmias) of succinylcholine are not mediated via direct activation of the autonomic ganglionic alpha3beta4 subtype because succinylcholine does not activate the neuronal nAChRs.
琥珀酰胆碱是临床麻醉和急救医学中使用最广泛的肌肉松弛剂之一。尽管其临床优势和心血管副作用已广为人知，但其在人烟碱型胆碱能受体系统中的作用机制仍有待阐明。本研究旨在探讨琥珀酰胆碱对人肌肉和神经元烟碱型乙酰胆碱受体（nAChR）亚型的影响。
将编码人肌肉和神经元nAChR亚基的信使RNA注射到非洲爪蟾卵母细胞中。使用多通道双电极电压钳装置研究天然配体乙酰胆碱或琥珀酰胆碱诱导的受体激活、脱敏和抑制作用。以峰值电流和净电荷测量反应。
琥珀酰胆碱浓度依赖性激活肌肉型nAChR，EC50值为10.8微摩尔（95%置信区间，9.8 - 11.9微摩尔），初始激活后，琥珀酰胆碱使肌肉型nAChR脱敏。在浓度高达1毫摩尔时，琥珀酰胆碱未激活神经元nAChR亚型α3β2、α3β4、α4β2或α7，并且在这些受体亚型上是弱抑制剂，IC50值高于100微摩尔。
琥珀酰胆碱激活肌肉型nAChR，随后脱敏。琥珀酰胆碱在临床相关浓度下不抑制突触前α3β2自身受体这一观察结果，为琥珀酰胆碱诱导的神经肌肉阻滞中典型的强直后增强缺失提供了一种可能的机制解释。最后，琥珀酰胆碱的心血管副作用（如快速性心律失常）不是通过自主神经节α3β4亚型的直接激活介导的，因为琥珀酰胆碱不激活神经元nAChR。
