Effects of (-) epigallocatechin-3-gallate on Na⁺ currents in rat dorsal root ganglion neurons

The natural product (-) epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. Dorsal root ganglion neurons are primary sensory neurons, and express tetrodotoxin-sensitive and tetrodotoxin-resistant Na⁺ currents, which are both actively involved in the generation and propagation of nociceptive signals. Effects of EGCG on tetrodotoxin-sensitive and tetrodotoxin-resistant Na⁺ currents in rat dorsal root ganglion neurons were investigated using the whole-cell variation of the patch-clamp techniques. EGCG inhibited both types of Na⁺ currents potently and in a concentration-dependent manner. The apparent dissociation constant, K_d, was estimated to be 0.74 and 0.80 μM for tetrodotoxin-sensitive and tetrodotoxin-resistant Na⁺ currents, respectively. (-) Epigallocatechin (EGC) was far less potent to inhibit Na⁺ currents than EGCG, suggesting that gallate moiety of EGCG is an important functional group to modulate Na⁺ currents. EGCG had little or no effect on the activation or steady-state inactivation voltage of either type of Na⁺ current. EGCG simply reduced the availability of Na⁺ channels for activation. Thus, EGCG appears to bind to resting Na⁺ channels to inhibit them. EGCG slowed the recovery of tetrodotoxin-sensitive Na⁺ current from inactivation. The property of EGCG to inhibit sensory Na⁺ currents can be utilized to develop an analgesic agent.