Differential responses of Ca-activated K channels to bradykinin in sensory neurons and F-11 cells.
Differential responses of Ca-activated K channels to bradykinin in sensory neurons and F-11 cells.
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感觉神经元和 F-11 细胞中 Ca 激活的 K 通道对缓激肽的差异反应。
DOI：
10.1152/ajpcell.1992.262.2.c453
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Oxford,GS
中科院分区：
文献类型：
--
作者：
Naruse,K;McGehee,DS;Oxford,GS
九肽缓激肽 (BK) 通过刺激内向阳离子电流来激发具有假定伤害感受功能的背根神经节 (DRG) 神经元子集。此外，BK 还能刺激各种细胞内信号传导途径，包括细胞内 Ca2+ 的升高。在 DRG 神经元 x 神经母细胞瘤杂交细胞 (F-11) 中，BK 会刺激细胞内 [Ca2+] 和内向电流的类似增加，但也会通过 Ca(2+) 激活的 K 通道引发大量瞬时外向电流。我们研究了两种细胞类型在单通道水平上外向电流反应差异表达的机制。尽管 K(Ca) 通道活性出现在暴露于 Ca2+ 的两个细胞的由内而外的斑块中，但应用于细胞附着斑块的斑块外膜的 BK 激活了 F-11 中的 K(Ca) 通道，但不激活 DRG 神经元。尽管单个 K(Ca) 通道在电导、电压依赖性和对四乙铵的敏感性方面在数量上相似，但它们对细胞内 Ca2+ 的敏感性不同。两个细胞中的通道激活至少需要四个 Ca2+ 离子，但 DRG 神经元的半最大激活发生在稍高的 [Ca2+] 处。 Ca2+ 剂量反应曲线的变化与通道开放概率的陡峭 [Ca2+] 依赖性相结合，使得 BK 诱导的内部 [Ca2+] 升高不太可能触发瞬态外向电流并导致 DRG 神经元超极化。
The nonapeptide bradykinin (BK) excites a subset of dorsal root ganglion (DRG) neurons with putative nociceptive functions by stimulating an inward cation current. In addition, BK stimulates various intracellular signaling pathways including an elevation of intracellular Ca2+. In a DRG neuron x neuroblastoma hybrid cell (F-11), BK stimulates similar increases in intracellular [Ca2+] and inward current but also elicits a large transient outward current through Ca(2+)-activated K channels. We have investigated the mechanisms underlying differential expression of outward current responses in the two cell types at the single channel level. Although K(Ca) channel activity appears in inside-out patches from both cells exposed to Ca2+, BK applied to the extrapatch membrane of cell-attached patches activates K(Ca) channels in F-11 but not DRG neurons. Whereas single K(Ca) channels are quantitatively similar in terms of conductance, voltage-dependence, and sensitivity to tetraethylammonium, they differ in sensitivity to intracellular Ca2+. Channel activation in both cells requires at least four Ca2+ ions, but half-maximal activation occurs at slightly higher [Ca2+] for DRG neurons. The shift in the Ca2+ dose-response curve combined with the steep [Ca2+] dependence of channel open probability makes it less likely that a BK-induced rise in internal [Ca2+] induced will trigger a transient outward current and resultant hyperpolarization in a DRG neuron.