Anesthesia and Pain Signal transmission and Role of Ion transporters at Spinal Cord

虽然已有许多研究表明局麻药作用于Na~+通道、K~+通道和Ca~(2+)通道，但离子转运体如Na~+-K~+-ATPase(钠泵)、Na~+-H~(++)交换器、Na~+-K~(++)-2CL共转运体在麻醉作用和痛觉信号传递中的作用尚不清楚。利用培养的PC12细胞株和脊髓导管动物模型，我们发现脊髓蛛网膜下腔注射其抑制剂具有明显的抗伤害性作用，Na+-K+-ATPase(Na泵)和Na+-H+交换器对脊髓水平的局部麻醉作用有显著的控制作用，而与Na+-K+-2CL共转运体的作用不明显。哇巴因和阿米洛利似乎不影响丝裂原活化蛋白激酶(MAPK)家族成员、细胞外信号调节蛋白激酶(ERKs)、PKC和PLC等信号分子。另一方面，局麻药影响这些信号分子。局麻药丁卡因通过MAPK家族的磷酸化诱导PC12细胞凋亡。ERK的激活保护细胞免于死亡，而JNK起相反的作用。丁卡因引起的中毒性钙离子内流似乎与细胞死亡有关，但阻断Na+通道和L型钙通道不太可能参与丁卡因对细胞凋亡信号分子的作用。

Although there have been many studies in which local anesthetic action has been examined on Na^+ channels and K^+ channels and Ca^(2+) channels, it has not been known as to roles of ion transporters such as Na^+-K^+ATPase ( Na pump ), Na^+-H^+ exchanger, Na^+-K^+-2CL cotranspoter on anesthetic action as well as pain signal transmission. Using cultured cell lines of PC12 cells and animal model with spinal catheter, we found that since their inhibitors administered into spinal subarachinoid caused significant antinociceptive action, Na^+-K^+ATPase ( Na pump ) and Na^+-H^+ exchanger would have significantrole in local anestheticaction at the spinal cord level, but not with Na^+-K^+-2CL cotranspoter. Oubabain and amiloride seem not to affect signaling molecules such as mitogen-activated protein kinase ( MAPK ) family members, extracellularsignal-regulatedkinases ( ERKs ), PKC, and PLC.On the other hand, local anesthetics affect such signaling molecules. Local anesthetic tetracaine induces apoptosis of PC12 cells via phosphorylation of MAPK family. ERK activation protects cells from death, but JNK plays the opposite role. Toxic Ca^<2+> influx caused by tetracaine seems to be responsible for apoptoticcell death, but blocking of Na^+ channels and L-type Ca^<2+> channels is unlikely involved in such tetracaine'saction on signaling molecules for apoptosis.