Protective actions of various local anesthetics against the membrane dysfunction produced by in vitro ischemia in rat hippocampal CA1 neurons.
Local anesthetics block not only the Na(+) but also the K(+) and Ca(2+) channels in the mammalian neurons. It is well known that lidocaine has neuroprotective actions against the ischemic insult of neurons in the central nervous system. In order to elucidate how other local anesthetics as well as lidocaine show the neuroprotective effects against in vitro ischemic insult, intracellular recordings were made from CA1 pyramidal neurons in rat hippocampal slices. Superfusion with the medium deprived of oxygen and glucose (in vitro ischemia) produced a rapid depolarization after 5 min of exposure. When the normal medium was immediately reintroduced after the rapid depolarization, the membrane depolarized further (persistent depolarization), the neurons showed no functional recovery. Pretreatment with tetracaine, bupivacaine, procaine, lidocaine, mepivacaine, or dibucaine (10 or 300 microM) prolonged the latency of the rapid depolarization, and most of the drugs partially restored the membrane potential toward the pre-exposure level after the reintroduction. Judging from the neuroprotective actions such as the prolongation and the potential recovery by these drugs, lidocaine, bupivacaine, and dibucaine are candidates for the therapeutic use against the ischemic insult. Suppression of the regenerative Na(+) conductance is somehow involved in the neuroprotective actions of local anesthetics.
Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Aya
A
Yamada
Eiichiro
E
Tanaka
Shuhei
S
Niiyama
Satoshi
S
Yamamoto
Miho
M
Hamada
Hideho
H
Higashi
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / 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*; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D018696:Neuroprotective Agents