Dale V M, Martin R J
Department of Preclinical Veterinary Sciences, R. (D.) S. V. S. Summerhall, University of Edinburgh.
Parasitology. 1995 May;110 ( Pt 4):437-48. doi: 10.1017/s0031182000064775.
The patch clamp technique was used to investigate the action of the anthelmintic drug, oxantel, on nicotinic acetylcholine receptor (nAChR) currents recorded from vesicles of the somatic muscle cells of the nematode parasite Ascaris suum. The amplitudes of the currents were analysed at different membrane potentials to determine the single channel conductance. Also the open and closed durations were measured to determine the kinetic properties of the activated channel. Oxantel activated single nAChR currents throughout a concentration range 10-100 microM, these currents were not observed with oxantel-free pipette solutions. The mean open time of the activated channels at a membrane potential of -75 mV and a concentration of 10 microM was 1.34 ms. At higher concentrations the open times were shorter and voltage sensitive, decreasing in duration on hyperpolarization, thus suggesting open channel block. The kinetics were analysed using a simple channel block model. The forward block rate, K + B, increased with increasing oxantel concentration but showed little increase as the membrane was hyperpolarized. K + B was 2.41 x 10(7) M-1 s-1 at -50 mV and 2.64 x 10(7) M-1 s-1 at -100 mV. The unblocking rate constant, K-B, did exhibit voltage sensitivity being 443.6 s-1 at -50 mV and 86.8 s-1 at -100 mV. Thus the blocking dissociation constant KB (= K-B/K + B) was 18.5 microM at -50 mV and 3.3 microM at -100 mV. The simple channel block scheme was found to be insufficient to explain fully the observations made; reasons for this are discussed.
采用膜片钳技术研究了驱虫药奥克太尔对线虫寄生虫猪蛔虫体肌细胞囊泡记录的烟碱型乙酰胆碱受体（nAChR）电流的作用。在不同膜电位下分析电流幅度以确定单通道电导。还测量了开放和关闭持续时间以确定激活通道的动力学特性。奥克太尔在10 - 100 microM的浓度范围内激活单个nAChR电流，无奥克太尔的移液管溶液未观察到这些电流。在膜电位为-75 mV和浓度为10 microM时，激活通道的平均开放时间为1.34 ms。在较高浓度下，开放时间较短且对电压敏感，超极化时持续时间缩短，因此提示开放通道阻滞。使用简单的通道阻滞模型分析动力学。正向阻滞速率K + B随奥克太尔浓度增加而增加，但膜超极化时增加很少。在-50 mV时K + B为2.41 x 10(7) M-1 s-1，在-100 mV时为2.64 x 10(7) M-1 s-1。去阻滞速率常数K-B确实表现出电压敏感性，在-50 mV时为443.6 s-1，在-100 mV时为86.8 s-1。因此，阻滞解离常数KB（= K-B/K + B）在-50 mV时为18.5 microM，在-100 mV时为3.3 microM。发现简单的通道阻滞方案不足以完全解释所做的观察结果；对此进行了讨论。
