Clinical dose of lidocaine destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron.
OBJECTIVE
Although lidocaine-induced cell toxicity has been reported, its mechanism is unclear. Cell size, morphological change, and membrane resistance are related to homeostasis and damage to the cell membrane; however, the effects of lidocaine on these factors are unclear. Using an identified LPeD1 neuron from Lymnaea stagnalis, we sought to determine how lidocaine affects these factors and how lidocaine is related to damage of the cell membrane.


METHODS
Cell size and morphological form were measured by a micrograph and imaging analysis system. Membrane potential and survival rate were obtained by intracellular recording. Membrane resistance and capacitance were measured by whole-cell patch clamp. Phosphatidyl serine and nucleic acid were double stained and simultaneously measured by annexin V and propidium iodide.


RESULTS
Lidocaine at a clinical dose (5-20 mM) induced morphological change (bulla and bleb) in the neuron and increased cell size in a concentration-dependent manner. Membrane potential was depolarized in a concentration-dependent manner. At perfusion of more than 5 mM lidocaine, the depolarized membrane potential was irreversible. Lidocaine decreased membrane resistance and increased membrane capacitance in a concentration-dependent manner. Both phosphatidyl serine and nucleic acid were stained under lidocaine exposure in a concentration-dependent manner.


CONCLUSIONS
A clinical dose of lidocaine greater than 5 mM destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron.
Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Miyazaki, Kiyotake-Cho, Miyazaki, 889-1692, Japan. pirotann@med.miyazaki-u.ac.jp
Shin
S
Onizuka
Ryuji
R
Tamura
Tetsu
T
Yonaha
Nobuko
N
Oda
Yuko
Y
Kawasaki
Tetsuro
T
Shirasaka
Seiji
S
Shiraishi
Isao
I
Tsuneyoshi
D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D025802:Electric Capacitance; D008012:Lidocaine / Q000633:toxicity*; D008195:Lymnaea; D008564:Membrane Potentials / Q000187:drug effects; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D000779:Anesthetics, Local; D017304:Annexin A5; D008012:Lidocaine