Differences in Mode of Action of Cochinchinenin A and B on Tetrodotoxin-Resistant Sodium Channels

Purpose: To explore the mechanism of antagonistic interaction between cochinchinenin A and B in modulating tetrodotoxin-resistant (TTR-X) sodium currents. Methods: The time variation of the effects induced by cochinchinenin A and B on the TTX-R sodium currents in dorsal root ganglion (DRG) neurons of rats were observed using whole-cell patch clamp technique. Based on pharmacological fundamental theory, the modes of action of cochinchinenin A and B on TTX-R channels were distinguished. Results: The scatter diagram which reflected the time variation of inhibition effect on TTX-R sodium currents induced by cochinchinenin A fitted well with occupancy theory equation (goodness of fit test, p > 0.05), while that of cochinchinenin B fitted well with rate theory equation (p > 0.05). The rate constants for combination and dissociation between cochinchinenin A and TTX-R sodium channel were (198.7 +/- 39.9) x 10(-3) and (41.1 +/- 6.2) x 10(-3) respectively; while corresponding values for combination and association between cochinchinenin B and TTX-R sodium channel were (99.9 +/- 16.8) x 10(-3) and (5.3 +/- 0.4) x 10(-3) respectively. Conclusion: The main cause of the antagonistic interaction between cochinchinenin A and B may be attributed to the different modes of their action on TTX-R sodium channels.