Lidocaine increases intracellular sodium concentration through a Na+-H+ exchanger in an identified Lymnaea neuron.| Authors: | Shin Onizuka, Toshiharu Kasaba, Ryuji Tamura, Mayumi Takasaki | | Language: | Eng. | | Date: | 18-04-2008 | | Journal: | Anesthesia and analgesia
(1526-7598)
| | Release: | Anesth Analg. 2008 May;106(5):1465-72, table of contents | |
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Abstract:
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BACKGROUND:
The intracellular sodium concentration ([Na(+)]in) is related to neuron excitability. For [Na(+)]in, a Na(+)-H(+) exchanger plays an important role, which is affected by intracellular pH ([pH]in). However, the effect of lidocaine on [pH]in and a Na(+)-H(+) exchanger is unclear. We used neuron from Lymnaea stagnalis to determine how lidocaine affects [pH]in, Na(+)-H(+) exchanger, and [Na(+)]in.
METHODS:
Intracellular sodium imaging by sodium-binding benzofuran isophthalate and intracellular pH imaging by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein were used to measure [Na(+)]in and [pH]in. Measurements for [Na(+)]in were made in normal, Na(+) free saline, with modified extracellular pH, and a Na(+)-H(+) exchanger antagonist [(5-N-ethyl-N-isopropyl amiloride, N-methylisopropylamiloride, and 5-(N,N-hexamethylene)-amiloride) pretreatment trials. Furthermore, [Na(+)]in and [pH]in were recorded simultaneously. From 0.1 to 10 mM, lidocaine, mepivacaine, bupivacaine, prilocaine, and QX-314 were evaluated.
RESULTS:
Lidocaine, mepivacaine, and prilocaine increased the [Na(+)]in in a dose-dependent manner. In contrast, QX-314 did not change the [Na(+)]in at each dose. In the Na(+) free saline or in the presence of each Na(+)-H(+) exchanger antagonist, lidocaine failed to increase [Na(+)]in. Lidocaine, mepivacaine, and prilocaine induced a significant decrease in [pH]in below baseline with an increase in [Na(+)]in. In contrast, QX-314 did not change the [pH]in. These results demonstrated that lidocaine increases [Na(+)]in through Na(+)-H(+) exchanger activated by intracellular acidification, which is induced by the proton trapping of lidocaine. This [Na(+)]in increase and [pH]in change induces cell toxicity.
CONCLUSION:
Lidocaine increases the [Na(+)] through a Na(+)-H(+) exchanger by proton trapping.
| | Copyright: | Anesthesia and analgesia
Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Miyazaki, Kiyotake-Cho, Miyazaki 889-1692, Japan. pirotann@med.miyazaki-u.ac.jp | | Full text: | | | Terms: | Amiloride, Anesthetics, Local, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Hydrogen-Ion Concentration, Lidocaine, Lymnaea, Mepivacaine, Microscopy, Fluorescence, Neurons, Prilocaine, Sodium, Sodium-Hydrogen Antiporter, Up-Regulation | | |
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