Reductions in external divalent cations evoke novel voltage-gated currents in sensory neurons.
Reductions in external divalent cations evoke novel voltage-gated currents in sensory neurons.
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DOI：
10.1371/journal.pone.0031585
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Taylor-Clark TE
中科院分区：
文献类型：
--
作者：
Bahia PK;Bennett ES;Taylor-Clark TE
二价阳离子调节细胞的兴奋性早已被认识到。感觉神经兴奋性对于与疼痛、感觉功能障碍和诱发反射相关的外周疾病至关重要。因此，我们研究了这些阳离子对分离的感觉神经活动的作用。从外部溶液中撤出Mg 2+和Ca 2+激活超过90%的解离小鼠感觉神经元。成像研究表明，Na+流入，然后引起去极化介导的激活电压门控Ca2+通道（CaV），这使得Ca2+流入后，二价重新引入。CaV（ω-芋螺毒素，硝苯地平）或NaV（河豚毒素，利多卡因）的抑制不能减少Na+内流。Ca2+内流受CaV抑制剂抑制，但不受TRPM7抑制（精胺）或钙池操纵通道抑制（SKF96365）的抑制。单独撤出Mg 2+或Ca 2+不能引起迷走神经感觉神经元中的阳离子流入。在分离的小鼠迷走神经感觉神经元的电生理学研究中，从外部溶液中撤出Mg 2+和Ca 2+会引起一个大的缓慢失活的电压门控电流（IDF），这不能通过增加负表面电位来解释。单独撤除Ca~（2+）不能引起IDF。有证据表明，IDF是一种非选择性阳离子电流。抑制NaV（利多卡因、利鲁唑）、CaV（西尼地平、硝苯地平）、KV（四乙铵、4-氨基吡啶）或TRPM7通道（精胺）不会降低IDF。总之，感觉神经元表达一种新的电压门控阳离子通道，可被外部Ca2+（IC50 ≤ 0.5 μ M）或Mg2+（IC50 ≤ 3 μ M）抑制。这种假定的通道的激活引起感觉神经元中的大量阳离子通量。
It has long been recognized that divalent cations modulate cell excitability. Sensory nerve excitability is of critical importance to peripheral diseases associated with pain, sensory dysfunction and evoked reflexes. Thus we have studied the role these cations play on dissociated sensory nerve activity. Withdrawal of both Mg2+ and Ca2+ from external solutions activates over 90% of dissociated mouse sensory neurons. Imaging studies demonstrate a Na+ influx that then causes depolarization-mediated activation of voltage-gated Ca2+ channels (CaV), which allows Ca2+ influx upon divalent re-introduction. Inhibition of CaV (ω-conotoxin, nifedipine) or NaV (tetrodotoxin, lidocaine) fails to reduce the Na+ influx. The Ca2+ influx is inhibited by CaV inhibitors but not by TRPM7 inhibition (spermine) or store-operated channel inhibition (SKF96365). Withdrawal of either Mg2+ or Ca2+ alone fails to evoke cation influxes in vagal sensory neurons. In electrophysiological studies of dissociated mouse vagal sensory neurons, withdrawal of both Mg2+ and Ca2+ from external solutions evokes a large slowly-inactivating voltage-gated current (IDF) that cannot be accounted for by an increased negative surface potential. Withdrawal of Ca2+ alone fails to evoke IDF. Evidence suggests IDF is a non-selective cation current. The IDF is not reduced by inhibition of NaV (lidocaine, riluzole), CaV (cilnidipine, nifedipine), KV (tetraethylammonium, 4-aminopyridine) or TRPM7 channels (spermine). In summary, sensory neurons express a novel voltage-gated cation channel that is inhibited by external Ca2+ (IC50∼0.5 µM) or Mg2+ (IC50∼3 µM). Activation of this putative channel evokes substantial cation fluxes in sensory neurons.
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