Niiyama Shuhei, Tanaka Eiichiro, Yamamoto Satoshi, Yasumoto Shingo, Kano Tatsuhiko, Higashi Hideho
Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Neurosci Res. 2002 Mar;42(3):231-41. doi: 10.1016/s0168-0102(01)00326-1.
Neuroprotective actions of local anesthetics, bupivacaine and tetracaine, against the irreversible membrane dysfunction induced by in vitro ischemia were investigated. Intracellular recordings were made from hippocampal CA1 neurons in rat brain slice preparations. Oxygen and glucose deprivation (in vitro ischemia) produced a rapid depolarization after approximately 5 min of exposure. When oxygen and glucose were reintroduced, the membrane depolarized further and reached at 0 mV: the membrane showed no functional recovery (irreversible membrane dysfunction). Pretreatment with tetracaine or bupivacaine significantly prolonged the latency of rapid depolarization. Bupivacaine, but not tetracaine, restored the membrane potential after the reintroduction of oxygen and glucose. Tetracaine and bupivacaine depressed both field postsynaptic potentials and presynaptic volleys. The drugs also reduced the dV/dt of Ca(2+)-dependent spikes and the rapid rise of Ca(2+) induced by in vitro ischemia. Compared with tetracaine, bupivacaine markedly suppressed the resting K(+) conductance and the ATP-sensitive and Ca(2+)-dependent K(+) conductances. Moreover, in the presence of tetraethylammonium (TEA), a majority of CA1 neurons impaled with Cs acetate-filled electrodes showed complete or partial recovery of the membrane potential after reintroducing oxygen and glucose. These results suggest that the neuroprotective action of bupivacaine is mainly due to the suppression of the K(+) conductances.
研究了局部麻醉药布比卡因和丁卡因对体外缺血诱导的不可逆膜功能障碍的神经保护作用。在大鼠脑片制备中对海马CA1神经元进行细胞内记录。氧和葡萄糖剥夺（体外缺血）在暴露约5分钟后产生快速去极化。当重新引入氧和葡萄糖时，膜进一步去极化并达到0 mV：膜没有显示出功能恢复（不可逆膜功能障碍）。用丁卡因或布比卡因预处理可显著延长快速去极化的潜伏期。布比卡因而非丁卡因在重新引入氧和葡萄糖后恢复了膜电位。丁卡因和布比卡因均降低了场突触后电位和突触前峰电位。这些药物还降低了钙依赖性动作电位的dV/dt以及体外缺血诱导的细胞内钙浓度的快速升高。与丁卡因相比，布比卡因显著抑制静息钾电导以及ATP敏感性钾电导和钙依赖性钾电导。此外，在存在四乙铵（TEA）的情况下，大多数用醋酸铯填充电极刺入的CA1神经元在重新引入氧和葡萄糖后显示膜电位完全或部分恢复。这些结果表明布比卡因的神经保护作用主要归因于对钾电导的抑制。
