Related Experiment Videos
Lidocaine suppresses the sodium current in Euhadra neurons which is mediated by cAMP-dependent protein
M Onozuka1, K Watanabe, S Imai
1Department of Anatomy (2nd Division), Gifu University School of Medicine, Japan.
Abstract:
The action of a local anesthetic, lidocaine, in association with the cyclic AMP (cAMP)-mediated intracellular biochemical process, was examined in identified Euhadra neurons. Lidocaine dose-dependently inhibited the inward current which was elicited by dibutyryl cAMP (db-cAMP) and isobutylmethylxanthine (IBMX). This inhibitory effect was transiently reversed by the intracellular injection of a catalytic subunit of a cAMP-dependent protein kinase. The inward current elicited by db-cAMP and IBMX was abolished by Na(+)-free saline but not by Ca(2+)-free saline. The data suggest that lidocaine is not acting directly on the Na+ channel, but acts at a level proximal to the catalytic subunit of cAMP-dependent protein kinase.
Insights
Lidocaine inhibits a cellular current involving cyclic AMP (cAMP) in snail neurons. This local anesthetic
Area of Science:
- Neuroscience
- Cellular Biology
- Pharmacology
Background:
- Cyclic AMP (cAMP) signaling pathways regulate numerous cellular functions.
- Local anesthetics like lidocaine can modulate neuronal activity through various mechanisms.
Purpose of the Study:
- To investigate the effect of lidocaine on cAMP-mediated intracellular processes in Euhadra neurons.
- To elucidate the specific site of action of lidocaine within the cAMP signaling pathway.
Main Methods:
- Patch-clamp electrophysiology was used to measure inward currents in Euhadra neurons.
- Neurons were treated with dibutyryl cAMP (db-cAMP) and isobutylmethylxanthine (IBMX) to elicit cAMP-mediated currents.
- Lidocaine's effects were assessed dose-dependently.
- Intracellular injections of a cAMP-dependent protein kinase catalytic subunit were performed.
- Ionic substitution experiments (Na+-free and Ca2+-free saline) were conducted.
Main Results:
- Lidocaine inhibited the db-cAMP and IBMX-elicited inward current in a dose-dependent manner.
- This inhibitory effect was transiently reversed by intracellular injection of the cAMP-dependent protein kinase catalytic subunit.
- The inward current was abolished in Na+-free saline but unaffected by Ca2+-free saline.
Conclusions:
- Lidocaine's action is not directly on the Na+ channel.
- Lidocaine appears to act proximally to the catalytic subunit of cAMP-dependent protein kinase.
- These findings provide insights into the molecular mechanisms of lidocaine's interaction with intracellular signaling pathways.