Abstract：
AbstractExtracellular calcium has been known to be required for in situ nematocyst discharge for more than 60 years, yet calcium\'s role in nematocyst discharge is poorly understood. Currently, we know that extracellular calcium plays at least two distinct roles in in situ nematocyst discharge. First, calcium plays a role in the triggering of discharge by physical contact, most likely involving transient receptor potential channels. Second, activated L-type calcium channels desensitize nematocyst discharge predisposed to discharge by stimulated chemoreceptors for N-acetylated sugars, such as N-acetylneuraminic acid (NANA). It is not known whether the stimulated NANA signaling pathway activates L-type channels electrogenically through membrane depolarization or directly by phosphorylation of the channel. We hypothesize that the activated NANA signaling pathway initiates desensitization by depolarizing cell membrane potentials to activate voltage-gated L-type calcium channels. Consistent with our hypothesis, we show that depolarization induced by blocking voltage-gated potassium channels with 4-aminopyridine selectively activates Ca2+ influx into tentacle ectodermal cells via L-type channels and inhibits in situ nematocyst discharge from chemosensitized anemones. Furthermore, preventing membrane depolarization with valinomycin or hyperpolarizing resting membrane potentials with low-potassium seawater suppresses NANA-induced Ca2+ influx, prevents desensitization of in situ nematocyst discharge, and enhances NANA sensitivity. Thus, changing resting membrane potentials modulates NANA sensitivity, and NANA-induced depolarization drives desensitization. We suggest that desensitization of the NANA signaling pathway occurs by a feedback pathway involving calcium channels that are activated by NANA-induced depolarization. Elucidating the desensitization pathway may suggest methods to protect or prevent public health cases of nematocyst stinging.
摘要：
60多年来，已知细胞外钙是原位线虫囊排出所必需的，然而，人们对钙在线虫囊排出中的作用知之甚少。目前,我们知道细胞外钙在原位线虫囊放电中至少有两种不同的作用。首先,钙在物理接触引发放电中起作用，最有可能涉及瞬时受体电位通道。第二,激活的L型钙通道使线虫囊放电脱敏，易于通过N-乙酰化糖的刺激化学感受器排出，例如N-乙酰神经氨酸(NANA)。尚不清楚受刺激的NANA信号传导途径是否通过膜去极化或直接通过通道的磷酸化以电化学方式激活L型通道。我们假设激活的NANA信号通路通过去极化细胞膜电位以激活电压门控L型钙通道来启动脱敏。与我们的假设一致，我们表明，通过用4-氨基吡啶阻断电压门控钾通道诱导的去极化选择性地激活Ca2通过L型通道流入触手外胚层细胞，并抑制化学致敏海葵的原位线虫囊排出。此外，用缬霉素防止膜去极化或用低钾海水超极化静息膜电位抑制NANA诱导的Ca2流入，防止原位线虫囊排出的脱敏，增强NANA灵敏度。因此，改变静息膜电位调节NANA敏感性，和NANA诱导的去极化驱动脱敏。我们建议NANA信号通路的脱敏是通过涉及由NANA诱导的去极化激活的钙通道的反馈通路发生的。阐明脱敏途径可能会提出保护或预防线虫囊刺痛公共卫生病例的方法。
