Lidocaine suppresses the anoxic depolarization and reduces the increase in the intracellular Ca2+ concentration in gerbil hippocampal neurons. 1997

K Liu, and N Adachi, and H Yanase, and K Kataoka, and T Arai
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Japan.

BACKGROUND The movement of ions, particularly Ca2+, across the plasma membrane of neurons is regarded as an initial element of the development of ischemic neuronal damage. Because the mechanism by which lidocaine protects neurons against ischemia is unclear, the effects of lidocaine on the ischemia-induced membrane depolarization, histologic outcome, and the change in the intracellular Ca2+ concentration in the gerbil hippocampus were studied. METHODS The changes in the direct-current potential shift in the hippocampal CA1 area produced by transient forebrain ischemia for 4 min were compared in animals given lidocaine (0.8 micromol administered intracerebroventricularly) 10 min before ischemia and those given saline. The histologic outcome was evaluated 7 days after ischemia by assessing delayed neuronal death in hippocampal CA1 pyramidal cells in these animals. In a second study, hypoxia-induced intracellular Ca2+ increases were evaluated by in vitro microfluorometry in gerbil hippocampal slices, and the effects of lidocaine (10, 50, and 100 microM) on the Ca2+ accumulation were examined. In addition, the effect of lidocaine (100 microM) drug perfusion with a Ca2+-free ischemia-like medium was investigated. RESULTS The preischemic administration of lidocaine delayed the onset of the ischemia-induced membrane depolarization (anoxic depolarization) and reduced its maximal amplitude. The histologic outcome was improved by the preischemic treatment with lidocaine. The in vitro hypoxia-induced increase in the intracellular concentration of Ca2+ was suppressed by the perfusion with lidocaine-containing mediums (50 and 100 microM), regarding the initiation and the extent of the increase. The hypoxia-induced intracellular Ca2+ elevation in the Ca2+-free condition was similar to that in the Ca2+-containing condition. Perfusion with lidocaine (100 microM) inhibited this elevation in the Ca2+-free condition. CONCLUSIONS Lidocaine helps protect neurons from ischemia by suppressing the direct-current potential shift, by inhibiting the release of Ca2+ from the intracellular Ca2+ stores, and by inhibiting the influx from the extracellular space.

UI MeSH Term Description Entries
D008012 Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE. Lignocaine,2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide,2-2EtN-2MePhAcN,Dalcaine,Lidocaine Carbonate,Lidocaine Carbonate (2:1),Lidocaine Hydrocarbonate,Lidocaine Hydrochloride,Lidocaine Monoacetate,Lidocaine Monohydrochloride,Lidocaine Monohydrochloride, Monohydrate,Lidocaine Sulfate (1:1),Octocaine,Xylesthesin,Xylocaine,Xylocitin,Xyloneural
D008297 Male Males
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002545 Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D005849 Gerbillinae A subfamily of the Muridae consisting of several genera including Gerbillus, Rhombomys, Tatera, Meriones, and Psammomys. Gerbils,Jird,Meriones,Psammomys,Rats, Sand,Gerbil,Jirds,Merione,Rat, Sand,Sand Rat,Sand Rats
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000779 Anesthetics, Local Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate. Anesthetics, Conduction-Blocking,Conduction-Blocking Anesthetics,Local Anesthetic,Anesthetics, Topical,Anesthetic, Local,Anesthetics, Conduction Blocking,Conduction Blocking Anesthetics,Local Anesthetics,Topical Anesthetics
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017136 Ion Transport The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions. Antiport,Ion Cotransport,Ion Exchange, Intracellular,Symport,Uniport,Active Ion Transport,Facilitated Ion Transport,Passive Ion Transport,Cotransport, Ion,Exchange, Intracellular Ion,Intracellular Ion Exchange,Ion Transport, Active,Ion Transport, Facilitated,Ion Transport, Passive,Transport, Active Ion,Transport, Ion

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