Protein kinase C mediates up-regulation of tetrodotoxin-resistant, persistent Na+ current in rat and mouse sensory neurones
Protein kinase C mediates up-regulation of tetrodotoxin-resistant, persistent Na+ current in rat and mouse sensory neurones
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DOI：
10.1113/jphysiol.2005.089771
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发表时间：
2005-09-15
影响因子：
5.5
通讯作者：
Baker, MD
中科院分区：
文献类型：
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作者：
Baker, MD
在P21大鼠、野生型成年小鼠和Na(V)1.8缺失小鼠培养的小（表观直径< 25 μ m）背根神经节（DRG）神经元中记录到Na(V)1.9引起的河豚毒素抗性（TTX-r）持续Na+电流。在常规的全细胞记录中，细胞内gtp - γ - s引起电流上调，这一作用被PKC假底物抑制剂PKC19-36抑制。25 μ m细胞内1-油基-2-乙酰基-sn-甘油（OAG）也上调了电流振幅，这与PKC的参与一致。在穿孔贴片记录中，phorbol 12-肉豆蔻酸酯13-乙酸酯（PMA）上调了电流，而膜渗透蛋白激酶A （PKA）的激活剂没有作用。PGE(2)没有明显上调电流。相反，PGE2和PKA激活均上调TTX-r Na+电流Na(V)1.8。细胞外ATP上调持续电流，平均表观K-d接近13 μ m，可能与P2Y受体激活一致。上调的数值模拟定性再现了感觉神经元放电特性的变化。PKC的激活似乎是gtp依赖性持续Na+电流上调的必要步骤。
The tetrodotoxin-resistant (TTX-r) persistent Na+ current, attributed to Na(V)1.9, was recorded in small (< 25 mu m apparent diameter) dorsal root ganglion (DRG) neurones cultured from P21 rats and from adult wild-type and Na(V)1.8 null mice. In conventional whole-cell recordings intracellular GTP-gamma-S caused current up-regulation, an effect inhibited by the PKC pseudosubstrate inhibitor, PKC19-36. The current amplitude was also up-regulated by 25 mu m intracellular 1-oleoyl-2-acetyl-sn-glycerol (OAG) consistent with PKC involvement. In perforated-patch recordings, phorbol 12-myristate 13-acetate (PMA) up-regulated the current, whereas membrane-permeant activators of protein kinase A (PKA) were without effect. PGE(2) did not acutely up-regulate the current. Conversely, both PGE2 and PKA activation up-regulated the major TTX-r Na+ current, Na(V)1.8. Extracellular ATP up-regulated the persistent current with an average apparent K-d near 13 mu m, possibly consistent with P2Y receptor activation. Numerical simulation of the up-regulation qualitatively reproduced changes in sensory neurone firing properties. The activation of PKC appears to be a necessary step in the GTP-dependent up-regulation of persistent Na+ current.