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大鼠肌管中胚胎型和成体型乙酰胆碱受体之间的动力学差异。

Kinetic differences between embryonic- and adult-type acetylcholine receptors in rat myotubes.

作者信息

Jaramillo F, Schuetze S M

机构信息

Department of Biological Sciences, Columbia University, New York, NY 10027.

出版信息

J Physiol. 1988 Feb;396:267-96. doi: 10.1113/jphysiol.1988.sp016962.

Abstract
  1. The burst structures of embryonic-type (low-gamma) and adult-type (high-gamma) nicotinic acetylcholine (ACh) receptors (AChRs) in rat myotubes were investigated with the patch clamp technique. The channels were activated with the agonists ACh and suberyldicholine (SubCh). 2. With either agonist, the distribution of burst durations showed two exponential components for both channel types: a 'long' component that corresponds to bursts of one or more openings and a 'brief' component that includes short, isolated openings. 3. For low-gamma channels, the percentage of all openings associated with the brief component decreased from approximately 40% at 10-100 nM-ACh to less than 10% at 10-100 microM-ACh. 4. Both high-gamma and low-gamma long bursts were interrupted by brief (30-90 microseconds) closures and longer (approximately 1 ms) transitions to a partially open (subconductance) state. The duration of brief closures and partial openings was relatively independent of the agonist, but their frequency within low-gamma bursts was 3-fold higher with SubCh than with ACh. 5. Brief closures are interpreted as transitions to a closed, doubly liganded state from which the channel can reopen. This model predicts that the channel opening rate is greater than 10,000 s-1 for both channel types at room temperature. 6. Estimates of the channel opening rate inferred from the rising phase of miniature end-plate currents recorded from rat soleus fibres are consistent with this interpretation. 7. Both high-gamma and low-gamma channels apparently operate via similar gating mechanisms. Differences in their gating behaviour can be explained in terms of faster kinetic rate constants for high-gamma channels.
摘要
  1. 采用膜片钳技术研究了大鼠肌管中胚胎型(低γ)和成年型(高γ)烟碱型乙酰胆碱(ACh)受体(AChRs)的爆发结构。通道用激动剂乙酰胆碱(ACh)和辛二酰胆碱(SubCh)激活。2. 无论使用哪种激动剂,两种通道类型的爆发持续时间分布均显示出两个指数成分:一个“长”成分对应于一个或多个开放的爆发,一个“短暂”成分包括短的、孤立的开放。3. 对于低γ通道,与短暂成分相关的所有开放的百分比从10 - 100 nM - ACh时的约40%降至10 - 100 μM - ACh时的不到10%。4. 高γ和低γ长爆发均被短暂(30 - 90微秒)关闭和更长(约1毫秒)的向部分开放(亚电导)状态的转变中断。短暂关闭和部分开放的持续时间相对独立于激动剂,但它们在低γ爆发中的频率,SubCh比ACh高3倍。5. 短暂关闭被解释为向关闭的、双配体状态的转变,通道可从该状态重新开放。该模型预测,在室温下两种通道类型的通道开放速率均大于10,000 s⁻¹。6. 从大鼠比目鱼肌纤维记录的微小终板电流上升相推断的通道开放速率估计与该解释一致。7. 高γ和低γ通道显然通过相似的门控机制运作。它们门控行为的差异可以用高γ通道更快的动力学速率常数来解释。

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