Effects of (−)-Gallocatechin-3-Gallate on Tetrodotoxin-Resistant Voltage-Gated Sodium Channels in Rat Dorsal Root Ganglion Neurons

Abstract

The (−)-gallocatechin-3-gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins. It has been shown that catechins have analgesic properties. Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant compared to other isoforms and functionally linked to nociception. In this study, the effects of GCG on tetrodotoxin-resistant Na+ currents were investigated in rat primary cultures of dorsal root ganglion neurons via the whole-cell patch-clamp technique. We found that 1 μM GCG reduced the amplitudes of peak current density of tetrodotoxin-resistant Na+ currents significantly. Furthermore, the inhibition was accompanied by a depolarizing shift of the activation voltage and a hyperpolarizing shift of steady-state inactivation voltage. The percentage block of GCG (1 μM) on tetrodotoxin-resistant Na+ current was 45.1% ± 1.1% in 10 min. In addition, GCG did not produce frequency-dependent block of tetrodotoxin-resistant Na+ currents at stimulation frequencies of 1 Hz, 2 Hz and 5 Hz. On the basis of these findings, we propose that GCG may be a potential analgesic agent.

Biophysical Characterization of Epigallocatechin-3-Gallate Effect on the Cardiac Sodium Channel Nav1.5

“…Indeed, in the presence of EGCG, the almost "normal" recovery from fast inactivation prevents an additional progressive accumulation of inactivated Na v 1.5, which represents the preferential binding state of EGCG. These findings are consistent with those obtained in other studies testing the effect of gallocatechin-3-gallate on the tetrodotoxin-resistant voltage-gated sodium channels in rat dorsal root ganglion neurons [32].…”

“…On the other hand, the observed shift of the steady-state of inactivation is consistent with what has been previously described for Na v 1.5 [30]. One should note that the EGCG effects on the other biophysical properties were mainly investigated on the neuronal Na v channels [32,35,36]. These published results are in concordance with the EGCG effect on the fast inactivation kinetics, and recovery from inactivation of the cardiac sodium channels.…”

“…Indeed, since Na v -βs are strong modulators of Na v 1.5 electrophysiological properties [14], the sensitivity of the cardiac sodium channel towards EGCG may be affected by the presence or absence of Na v -β1. Furthermore, conducting experiments at elevated temperatures may induce the degradation of EGCG and its epimerization to gallocatechin-3-gallate (GCG) [31], which could trigger different biophysical modifications of I Na current as it was shown in rat dorsal root ganglion neurons [32]. On the other hand, under the same conditions, the activity of EGCG on Na v 1.5 could be altered as it was described for other I Na inhibitors such as flecainide, ajmaline, and ranolazine [33,34].…”