OXANTEL-ACTIVATED SINGLE-CHANNEL CURRENTS IN THE MUSCLE MEMBRANE OF ASCARIS-SUUM
OXANTEL-ACTIVATED SINGLE-CHANNEL CURRENTS IN THE MUSCLE MEMBRANE OF ASCARIS-SUUM
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DOI：
10.1017/s0031182000064775
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发表时间：
1995-05-01
期刊：
影响因子：
2.4
通讯作者：
MARTIN, RJ
中科院分区：
文献类型：
--
作者：
DALE, VME;MARTIN, RJ
膜片钳技术用于研究驱虫药 oxantel 对从线虫寄生虫猪蛔虫体肌细胞囊泡记录的烟碱乙酰胆碱受体 (nAChR) 电流的作用。分析不同膜电位下的电流幅度以确定单通道电导。还测量打开和关闭持续时间以确定激活通道的动力学特性。 Oxantel 在 10-100 μM 浓度范围内激活单个 nAChR 电流，使用不含 oxantel 的移液器溶液未观察到这些电流。在膜电位为-75 mV、浓度为10 μM 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，超极化持续时间减少，因此表明开放通道阻塞。使用简单的通道块模型分析动力学。正向阻断率 K+B 随着 oxantel 浓度的增加而增加，但随着膜超极化而几乎没有增加。 K+B 在-50 mV 时为2.41 x 10(7) M(-1)s(-1)，在-100 mV 时为2.64 x 10(7) M(-1)s(-1)。解锁速率常数 K-B 确实表现出电压灵敏度，-50 mV 时为 443.6 s(-1)，-100 mV 时为 86.8 s(-1)。因此，阻断解离常数KB(=K-B/K+B)在-50mV时为18.5μM，在-100mV时为3.3μM。人们发现简单的通道块方案不足以充分解释所进行的观察；对此的原因进行了讨论。
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 mu M, 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 mu M 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 mu M at -50 mV and 3.3 mu M at -100 mV. The simple channel block scheme was found to be insufficient to explain fully the observations made; reasons for this are discussed.