Brezina V, Evans C G, Weiss K R
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029.
J Neurosci. 1994 Jul;14(7):4393-411. doi: 10.1523/JNEUROSCI.14-07-04393.1994.
A major goal of neuroscience is to identify the neural and cellular mechanisms of behavior and its plasticity. Progress toward this goal has come particularly from work with a small number of tractable model preparations. One of these is the simple neuromuscular circuit consisting of the accessory radula closer (ARC) muscle of the mollusk Aplysia californica and its innervating motor and modulatory neurons. Contraction of the ARC muscle underlies a component of Aplysia feeding behavior, and plasticity of the behavior is in large part due to modulation of the amplitude and duration of the contractions of the muscle by a variety of modulatory neurotransmitters and peptide cotransmitters, among them the small cardioactive peptides (SCPs), myomodulins (MMs), and serotonin (5-HT). We have studied single dissociated ARC muscle fibers in order to determine whether modulation of membrane ion currents in the muscle might underlie these effects. First, we confirmed that the dissociated fibers were functionally intact: just as with the whole ARC muscle, their contractions were potentiated by 5-HT and SCPB and potentiated as well as depressed by MMA, and their cAMP content was greatly elevated by 5-HT, SCPA and SCPB, and to a lesser extent by MMA and MMB. Next, using voltage-clamp techniques, we found that two ion currents present in the fibers were indeed modulated. The fibers possess a dihydropyridine-sensitive, high-threshold "L"-type Ca current. This current was enhanced by the modulators that potentiate ARC-muscle contractions--5-HT, SCPA and SCPB, and MMA and MMB--but not by buccalinA, a modulator that does not act directly on the ARC muscle. All of the potentiating modulators, as well as elevation of cAMP in the fibers by forskolin or a cAMP analog, maximally enhanced the current about twofold and mutually occluded each other's effects. Since the Ca current supplies Ca2+ necessary for contraction of the muscle, the enhancement of the current is a good candidate to be a major mechanism of the potentiation of the contractions. In the following article we report that the modulators also, to different degrees, activate a distinctive K current and thereby depress the contractions. Net potentiation or depression then depends on the balance between the relative strengths of the modulation of the two ion currents.
神经科学的一个主要目标是确定行为及其可塑性的神经和细胞机制。在实现这一目标方面取得的进展尤其来自于对少数易于处理的模型标本的研究。其中之一是由加州海兔的副齿舌闭肌（ARC）及其支配的运动和调节神经元组成的简单神经肌肉回路。ARC肌肉的收缩是海兔进食行为的一个组成部分，而该行为的可塑性在很大程度上归因于多种调节性神经递质和肽类共递质对肌肉收缩幅度和持续时间的调节，其中包括小的心脏活性肽（SCPs）、肌调节素（MMs）和5-羟色胺（5-HT）。我们研究了单个分离的ARC肌肉纤维，以确定肌肉中膜离子电流的调节是否可能是这些效应的基础。首先，我们证实分离的纤维在功能上是完整的：就像整个ARC肌肉一样，它们的收缩被5-HT和SCPB增强，被MMA增强和抑制，并且它们的cAMP含量被5-HT、SCPA和SCPB大大提高，被MMA和MMB提高的程度较小。接下来，使用电压钳技术，我们发现纤维中存在的两种离子电流确实受到了调节。这些纤维具有一种对二氢吡啶敏感的、高阈值的“L”型钙电流。该电流被增强ARC肌肉收缩的调节剂——5-HT、SCPA和SCPB，以及MMA和MMB——增强，但不被不直接作用于ARC肌肉的调节剂buccalinA增强。所有增强性调节剂，以及通过福斯可林或一种cAMP类似物使纤维中的cAMP升高，都使电流最大增强约两倍，并且相互抵消彼此的作用。由于钙电流为肌肉收缩提供所需的Ca2+，电流的增强很可能是收缩增强的主要机制之一选。在接下来的文章中，我们报道这些调节剂也不同程度地激活一种独特的钾电流，从而抑制收缩。净增强或抑制则取决于两种离子电流调节的相对强度之间的平衡。
