Lidocaine suppresses the sodium current in Euhadra neurons which is mediated by cAMP-dependent protein phosphorylation.
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.
Onozuka
M
M
Department of Anatomy (2nd Division), Gifu University School of Medicine, Japan.
Watanabe
K
K
Imai
S
S
Nagasaki
S
S
Yamamoto
T
T
D015056:1-Methyl-3-isobutylxanthine / Q000037:antagonists & inhibitors; D000818:Animals; D003994:Bucladesine / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D012908:Snails; D015222:Sodium Channels / Q000187:drug effects*
D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D003994:Bucladesine; D008012:Lidocaine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015056:1-Methyl-3-isobutylxanthine