Inhibition of acid sensing ion channel currents by lidocaine in cultured mouse cortical neurons

Jun Lin, Xiangping Chu, Samaneh Maysami, Minghua Li, Hongfang Si, James E. Cottrell, Roger P. Simon, Zhigang Xiong

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Lidocaine is a local anesthetic that has multiple pharmacological effects including antiarrhythmia, antinociception, and neuroprotection. Acid sensing ion channels (ASICs) are proton-gated cation channels that belong to the epithelial sodium channel/degenerin superfamily. Activation of ASICs by protons results in sodium and calcium influx. ASICs have been implicated in various physiological processes including learning/memory, nociception, and in acidosis-mediated neuron injury. In this study, we examined the effect of lidocaine on ASICs in cultured mouse cortical neurons. Methods: ASIC currents were activated and recorded using a whole-cell patch-clamp technique in cultured mouse cortical neurons. The effects of lidocaine at different concentrations were examined. To determine whether the inhibition of lidocaine on ASIC currents is subunit specific, we examined the effect of lidocaine on homomeric ASIC1a and ASIC2a currents expressed in Chinese hamster ovary cells. Results: Lidocaine significantly inhibits the ASIC currents in mouse cortical neurons. The inhibition was reversible and dose dependent. A detectable effect was noticed at a concentration of 0.3 mM lidocaine. At 30 mM, ASIC current was inhibited by approximately 90%. Analysis of the complete dose-response relationship yielded a half-maximal inhibitory concentration of 11.79 ± 1.74 mM and a Hill coefficient of 2.7 ± 0.5 (n = 10). The effect is rapid and does not depend on pH. In Chinese hamster ovary cells expressing different ASIC subunits, lidocaine inhibits the ASIC1a current without affecting the ASIC2a current. Conclusion: ASIC currents are significantly inhibited by lidocaine. Our finding reveals a new pharmacological effect of lidocaine in neurons.

Original languageEnglish (US)
Pages (from-to)978-981
Number of pages4
JournalAnesthesia and Analgesia
Volume112
Issue number4
DOIs
StatePublished - Jan 1 2011

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Acid Sensing Ion Channels
Lidocaine
Neurons
Cricetulus
Protons
Degenerin Sodium Channels
Ovary
Inhibition (Psychology)
Pharmacology
Physiological Phenomena
Epithelial Sodium Channels
Nociception
Patch-Clamp Techniques
Acidosis
Local Anesthetics
Cations

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Inhibition of acid sensing ion channel currents by lidocaine in cultured mouse cortical neurons. / Lin, Jun; Chu, Xiangping; Maysami, Samaneh; Li, Minghua; Si, Hongfang; Cottrell, James E.; Simon, Roger P.; Xiong, Zhigang.

In: Anesthesia and Analgesia, Vol. 112, No. 4, 01.01.2011, p. 978-981.

Research output: Contribution to journalArticle

Lin, Jun ; Chu, Xiangping ; Maysami, Samaneh ; Li, Minghua ; Si, Hongfang ; Cottrell, James E. ; Simon, Roger P. ; Xiong, Zhigang. / Inhibition of acid sensing ion channel currents by lidocaine in cultured mouse cortical neurons. In: Anesthesia and Analgesia. 2011 ; Vol. 112, No. 4. pp. 978-981.
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abstract = "Background: Lidocaine is a local anesthetic that has multiple pharmacological effects including antiarrhythmia, antinociception, and neuroprotection. Acid sensing ion channels (ASICs) are proton-gated cation channels that belong to the epithelial sodium channel/degenerin superfamily. Activation of ASICs by protons results in sodium and calcium influx. ASICs have been implicated in various physiological processes including learning/memory, nociception, and in acidosis-mediated neuron injury. In this study, we examined the effect of lidocaine on ASICs in cultured mouse cortical neurons. Methods: ASIC currents were activated and recorded using a whole-cell patch-clamp technique in cultured mouse cortical neurons. The effects of lidocaine at different concentrations were examined. To determine whether the inhibition of lidocaine on ASIC currents is subunit specific, we examined the effect of lidocaine on homomeric ASIC1a and ASIC2a currents expressed in Chinese hamster ovary cells. Results: Lidocaine significantly inhibits the ASIC currents in mouse cortical neurons. The inhibition was reversible and dose dependent. A detectable effect was noticed at a concentration of 0.3 mM lidocaine. At 30 mM, ASIC current was inhibited by approximately 90{\%}. Analysis of the complete dose-response relationship yielded a half-maximal inhibitory concentration of 11.79 ± 1.74 mM and a Hill coefficient of 2.7 ± 0.5 (n = 10). The effect is rapid and does not depend on pH. In Chinese hamster ovary cells expressing different ASIC subunits, lidocaine inhibits the ASIC1a current without affecting the ASIC2a current. Conclusion: ASIC currents are significantly inhibited by lidocaine. Our finding reveals a new pharmacological effect of lidocaine in neurons.",
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