Abstract
The synthetic ciguatoxin, CTX3C has been shown to activate TTX-sensitive sodium channels (Nav1.2, 1.4 and 1.5) by accelerating activation kinetics and shifts the activation curve to the hyperpolarizing direction1. In this study, we examined the effects of CTX3C on one of TTX-resistant (TTX-R) sodium channels, Nav1.8 Na+ channels. There are several evidences that Nav1.8 is related to hyperexcitability observed in primary afferent neurons following nerve and tissue injury. Thus, Nav1.8 has been considered to be the cause of hyperalgesia or neuropathic pain. On the other hand, ciguatoxin causes ciguatera, which is widespread fish poisoning and often presents neurotoxic symptoms, hyperalgesia or allodynia. We found 100 nM CTX3C is sufficient to modulate voltage-elicited currents of Nav1.4 expressed in HEK293 cells at -100 mV, 10 times less dose are required than at -140 mV. However, no currents were observed without stimulus. Sustained currents of Nav1.8, expressed in ND7-23 cells, were induced by application of 100 nM CTX3C without stimulus. The induced sustained currents were activated by depolarization to -80 mV, deactivated by hyperpolarization to -120 mV. These electrophysiological properties of Nav1.8 well correlate with the sensory neurological symptoms associated with ciguatera fish poisoning. REFERENCE1. Yamaoka, K., M. Inoue, et al. (2004). Br J Pharmacol 142(5): 879-89. [J Physiol Sci. 2007;57 Suppl:S78]
