Bupivacaine, but not tetracaine, protects against the in vitro ischemic insult of rat hippocampal CA1 neurons.
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+)](i) 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.
Niiyama
Shuhei
S
Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Tanaka
Eiichiro
E
Yamamoto
Satoshi
S
Yasumoto
Shingo
S
Kano
Tatsuhiko
T
Higashi
Hideho
H
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D002045:Bupivacaine / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013748:Tetracaine / Q000494:pharmacology*
D000779:Anesthetics, Local; D018696:Neuroprotective Agents; D026902:Potassium Channel Blockers; D013748:Tetracaine; D002118:Calcium; D002045:Bupivacaine