Ketamine blockage of both tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels of rat dorsal root ganglion neurons.
Ketamine, a general anesthetic, has been reported to block sodium channels. Two types of Na(+) channels, tetrodotoxin (TTX)-sensitive (TTX-s) and TTX-resistant (TTX-r), are expressed in dorsal root ganglion (DRG) neurons. The present study was to investigate the effects of ketamine on both types, particularly on TTX-r channels, using whole-cell patch-clamp recordings in dissociated rat DRG neurons. In addition to confirming ketamine-induced blockage of TTX-s Na(+) current, we showed for the first time that ketamine blocked TTX-r Na(+) channels on small DRG neurons in dose-dependent and use-dependent manner. Half-maximal inhibitory concentration (IC(50)) was 866.2 microM for TTX-r Na(+) channels. TTX-r Na(+) channels were more sensitive to ketamine in inactivated state (IC(50) = 314.8 microM) than in resting state (IC(50) = 866.2 microM). IC(50) was 146.7 microM for TTX-s Na(+) current. Activation and inactivation properties of both TTX-s and TTX-r Na(+) channels were affected by ketamine. Since TTX-r Na(+) channels were preferentially expressed in small DRG neurons known as nociceptors, blockage of TTX-r Na(+) channels by ketamine may result in reducing nociceptive signals conducting to the spinal cord. Moreover, both TTX-r and TTX-s Na(+) channels would be non-selectively blocked by ketamine at high concentration, suggesting that the high dose of ketamine might produce an action of local anesthesia.
Shanghai Institute of Physiology, Chinese Academy of Sciences, P. R., Shanghai, China.
Z S
ZS
Zhou
Z Q
ZQ
Zhao
D000200:Action Potentials / Q000187:drug effects; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002469:Cell Separation; D048429:Cell Size; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
D000778:Anesthetics, Dissociative; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D007649:Ketamine; D012964:Sodium; D002211:Capsaicin