Effects of anesthetics on ATP sensitive K channels in rat substantia nigra dopamine neurons.

虽然一些全身麻醉药对心肌细胞和平滑肌细胞的ATP敏感性钾通道（KATP）具有调节作用，但它们对神经元KATP的影响尚不清楚。本文采用膜片钳技术研究了两种不同麻醉剂对大鼠黑质致密部多巴胺神经元ATP敏感性钾通道（KATP）的影响，用含2mM、2 1 mM或0 mM. Daizoxide或通过从移液管溶液中排除ATP的细胞内ATP耗竭使神经元超极化并消除自发活动以甲苯磺丁脲敏感的方式潜在击发。异氟烷是一种挥发性麻醉剂，在细胞内ATP存在下诱导轻微去极化，但在2.2 MAC当量ATP耗尽后不会改变膜电位。1 MAC当量异氟烷在两种条件下均未引起显著影响。蛋白激酶C的激活不影响异氟烷的作用，这与先前对心脏肌膜KATP的研究不同。氯胺酮是一种静脉麻醉剂，|在ATP 2 mM的存在下，膜电位，但部分拮抗超极化和外向电流引起的ATP耗竭在100 μM。这些结果表明，异氟醚对这些神经元中的KATP没有显著影响，而氯胺酮对激活的KATP具有阻断作用。

While it is shown that some of general anesthetics have modulatory effects on ATP sensitive K channels (KATP) in cardiac myocytes and smooth muscle cells, their effects on neuronal KATP are poorly understood. We have investigated effects of two different anesthetics on neuronal ATP sensitive K channels (KATP) in rat dopamine neurons located in substantia nigra pars compacts, using a slice patch technique.We measured the membrane potential and current with the pipette solutions containing ATP either 2 mM, 1 mM or 0 mM. Daizoxide or intracellular ATP depletion by exclusion of ATP from the pipette solution hyperpolarized the neurons and abolished spontaneous action potential firings in a tolbutamide sensitive manner. Isoflurane, a volatile anesthetic, induced a slight depolarization in the presence of intracellular ATP but did not alter the membrane potential after ATP was depleted at 2.2 MAC equivalent Isoflurane at 1 MAC equivalent caused no significant effects in either conditions. Activation of protein kinase C did not influence the effects of isoflurane, unlike to a previous study on cardiac sarcolemmal KATP. Ketamine, an intravenous anesthetic, did not affect the| membrane potential in the presence of ATP 2 mM but partially antagonized hyperpolarization and the outward current caused by ATP depletion at 100 μM. or above.These results suggest that isoflurane has no significant effects on KATP but ketamine has a blocking action on activated KATP in these neurons.