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 microM 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.
Kim
Tae Hoon
TH
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea.
Lim
Jae-Min
JM
Kim
Sung Su
SS
Kim
Jungho
J
Park
Mijung
M
Song
Jin-Ho
JH
D018712:Analgesics, Non-Narcotic / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D015222:Sodium Channels; D013779:Tetrodotoxin; D002392:Catechin; C045651:epigallocatechin gallate