Contribution of endoplasmic reticulum Ca2+ regulatory mechanisms to the inflammation-induced increase in the evoked Ca2+ transient in rat cutaneous dorsal root ganglion neurons.
Contribution of endoplasmic reticulum Ca2+ regulatory mechanisms to the inflammation-induced increase in the evoked Ca2+ transient in rat cutaneous dorsal root ganglion neurons.
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DOI：
10.1016/j.ceca.2013.04.002
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发表时间：
2013-07
期刊：
影响因子：
4
通讯作者：
Gold MS
中科院分区：
文献类型：
--
作者：
Scheff NN;Lu SG;Gold MS
持续性炎症导致假定的伤害性皮肤背根神经节（DRG）神经元中高K+诱发的Ca 2+瞬变的幅度和持续时间增加。本研究的目的是确定Ca 2+诱导的Ca 2+释放（CICR）的募集是否有助于这些炎症诱导的变化。急性分离，逆行标记的皮肤DRG神经元从幼稚和完全弗氏佐剂发炎的成年雄性Sprague道利大鼠进行了研究与比率显微荧光法。Ryanodine仅减弱炎症大鼠神经元中高K+诱发的Ca 2+瞬变的持续时间，但不减弱其幅度。然而，炎症对ryanodine诱导的阻断咖啡因诱发的Ca 2+瞬变的效力或功效没有显著影响，或者对肌质内质网ATP酶（SERCA）抑制对高K+诱发的Ca 2+瞬变的影响也没有显著影响。此外，虽然没有变化的幅度，炎症诱导的咖啡因诱发的Ca 2+瞬变的持续时间增加，只观察到与长期的咖啡因应用。与高K+诱发的Ca 2+瞬变相反，没有证据表明直接线粒体参与或Ca 2+挤出机制，Na+/Ca 2+交换，对咖啡因诱发的Ca 2+瞬变，SERCA的阻断只增加了这种瞬变的持续时间。这些结果表明，在皮肤伤害性DRG神经元内，胞质内Ca 2+通过流入和释放而增加的Ca 2+调节结构域是高度分离的。此外，我们的研究结果表明，无论是CICR机制的变化，也不是Ca 2+内流和CICR之间的耦合是主要负责炎症诱导的变化，诱发的Ca 2+瞬态。
Persistent inflammation results in an increase in the magnitude and duration of high K+-evoked Ca2+ transients in putative nociceptive cutaneous dorsal root ganglion (DRG) neurons. The purpose of the present study was to determine whether recruitment of Ca2+-induced Ca2+ release (CICR) contributes to these inflammation-induced changes. Acutely dissociated, retrogradely labeled cutaneous DRG neurons from naïve and complete Freund’s adjuvant inflamed adult male Sprague Dawley rats were studied with ratiometric microfluorimetry. Ryanodine only attenuated the duration but not magnitude of the high K+-evoked Ca2+ transient in neurons from inflamed rats. However, there was no significant impact of inflammation on the potency or efficacy of ryanodine-induced block of the caffeine-evoked Ca2+ transient, or the impact of sarco-endoplasmic reticulum ATPase (SERCA) inhibition on the high K+-evoked Ca2+ transient. Furthermore, while there was no change in the magnitude, an inflammation-induced increase in the duration of the caffeine-evoked Ca2+ transient was only observed with a prolonged caffeine application. In contrast to the high K+-evoked Ca2+ transient, there was no evidence of direct mitrochondrial involvement or that of the Ca2+ extrusion mechanism, the Na+/Ca2+ exchanger, on the caffeine-evoked Ca2+ transient, and block of SERCA only increased the duration of this transient. These results indicate the presence of Ca2+ regulatory domains in cutaneous nociceptive DRG neurons within which cytosolic Ca2+ increased via influx and release are highly segregated. Furthermore, our results suggest that changes in neither CICR machinery nor the coupling between Ca2+ influx and CICR are primarily responsible for the inflammation-induced changes in the evoked Ca2+ transient.