High capability of pentagalloylglucose (Pgg) in inhibiting multiple types of membrane ionic currents

Pentagalloyglucose (PGG, penta-O-galloyl-β-d-glucose; 1,2,3,4,6-pentagalloyl glucose), a pentagallic acid ester of glucose, is recognized to possess anti-bacterial, anti-oxidative and anti-neoplastic activities. However, to what extent PGG or other polyphenolic compounds can perturb the magnitude and/or gating of different types of plasmalemmal ionic currents remains largely uncertain. In pituitary tumor (GH₃) cells, we found out that PGG was effective at suppressing the density of delayed-rectifier K⁺ current (I_K(DR) ) concentration-dependently. The addition of PGG could suppress the density of proton-activated Cl⁻ current (I_PAC) observed in GH₃ cells. The IC₅₀ value required for the inhibitory action of PGG on I_K(DR) or I_PAC observed in GH₃ cells was estimated to be 3.6 or 12.2 µM, respectively, while PGG (10 µM) mildly inhibited the density of the erg-mediated K⁺ current or voltage-gated Na⁺ current. The presence of neither chlorotoxin, hesperetin, kaempferol, morin nor iberiotoxin had any effects on I_PAC density, whereas hydroxychloroquine or 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5yl)oxy] butanoic acid suppressed current density effectively. The application of PGG also led to a decrease in the area of voltage-dependent hysteresis of I_PAC elicited by long-lasting isosceles-triangular ramp voltage command, suggesting that hysteretic strength was lessened in its presence. In human cardiac myocytes, the exposure to PGG also resulted in a reduction of ramp-induced I_K(DR) density. Taken literally, PGG-perturbed adjustment of ionic currents could be direct and appears to be independent of its anti-oxidative property.