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 (IC50) was 866.2 mu M for TTX-r Na+ channels. TTX-r Na+ channels were more sensitive to ketamine in inactivated state (IC50 = 314.8 mu M) than in resting state (IC50 = 866.2 mu M). IC50 was 146.7 mu M 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. (C) 2000 Elsevier Science Inc.