Anesthesia and Pain Signal transmission and Control Mechanisms of Ion transporters

虽然离子转运体在活细胞和生物体中的作用是至关重要的，但从麻醉和疼痛传递的角度研究离子转运体的作用的研究还很少。因为我们已经通过大鼠的活体实验研究了局麻药对Na~+-K~+-ATPase(钠泵)活性的影响。我们发现，由于它们的抑制剂作用于脊髓蛛网膜下腔具有显著的抗伤害性作用，Na~+-K~+-ATPase(Na泵)和Na~+-H~+交换器在脊髓水平的局部麻醉作用中起重要作用，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、细胞外信号调节激酶(ERKs)、PKC和PLC等信号分子。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。利用大鼠背根神经节的神经元活性，我们还发现NMDA受体拮抗剂氯胺酮和异丙苯地尔以及1c类抗心律失常药氟卡胺和匹西卡胺也能影响TTX抵抗的Na+通道活动。咪达唑仑通过使用心肌细胞和静脉麻醉药，通过抑制p38丝裂原激活蛋白激酶来抑制凝血酶诱导的热休克蛋白27的磷酸化。我们的研究表明，临床上使用的局麻药和静脉麻醉药都可以通过调节细胞内信号分子来影响离子通道和离子转运体。结果提示，这种作用似乎在麻醉作用和疼痛传递中起着一定的作用。

Although the action of ion-transporters is vital in living cell and organisms, there have been only few studies in which roles of ion-transporters have been investigated on the aspect of anesthesia and pain transmission. Since we have examined how local anesthetics could affect Na^+-K^+ATPase (Na pump) activity using in vivo experiments of rats. 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 significant role in local anesthetic action 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, extracellular signal-regulated kinases (ERKs), PKC, and PLC. 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 apoptotic cell death, but blocking of Na^+ channels and L-type Ca^<2+> channels is unlikely involved in such tetracaine's action on signaling molecules for apoptosis. Using neuronal acitivity of rat's dorsal root ganglion we also found that NMDA receptor antagonists such as ketamine and ifenprodil, as well as Class 1c antiarrhythmics such as flecainide and pilsicainide could also affect TTX resistant Na+ channel activity. Using cardiac myocytes, intravenous anesthetics, midazolam suppresses thrombin-induced heat shock protein 27 phosphorylation through inhibition of p38 mitogen-activated protein kinaseOur studies indicate that local anesthetics as well as intravenous anesthetics used clinically could affect ion channel and ion-transporters via modulation of intracellular signaling molecules. The results suggested that such action would seem to play some roles in anesthetic action and pain transmission.