In contrast, under external Ca2+-free conditions, the same stimuli failed to affect [Ca2+](i) but caused an increase in pH(i), the magnitude of which was related to the [K+](radical anion) applied and the change in membrane potential. Consistent with the properties of 9(H)(+)S in other cell types, the magnitude of the rise in pH, observed in the absence of external Ca2+ was not

affected by the removal of external Na+ but was sensitive to external Zn2+ and temperature and was dependent on the A-1210477 molecular weight measured transmembrane pH gradient (Delta pH(memb)). Increasing Delta pH(memb) by pretreatment with carbonylcyanide-p-trifluoromethoxyphenylhydrazone augmented both the high-[K+](radical anion)-evoked rise in pH(i) and the Zn2+-sensitive component of the rise in pH(i), suggestive of increased acid extrusion via a g(H)(+). The inhibitory effect of Zn2+ at a given Delta pH(memb) was further enhanced by increasing pH. from 7.35-7.8, consistent with a pH.-dependent inhibition of the putative g(H)(+) by Zn2+. Under conditions

designed to isolate H+ currents, a voltage-dependent outward current was recorded from whole-cell patch-clamped neurons. Although the outward current appeared to show some selectivity for protons, it was not sensitive to Zn2+ or temperature and the H+-selective component could not be separated from a larger conductance of unknown selectivity. Nonetheless, taken together, the results suggest that a Zn2+-sensitive proton conductive pathway is present in rat hippocampal neurons and contributes to H+ efflux under depolarizing AL3818 cell line conditions. (c) 2008 IBRO. Published by Elsevier Ltd. CCI-779 All rights reserved.”
“Leaves

from Phyllanthus muellerianus (Kuntze) Exell. are traditionally used for wound healing in Western Africa. Aqueous extracts of dried leaves recently have been shown to stimulate proliferation of human keratinocytes and dermal fibroblasts. Within bioassay-guided fractionation the ellagitannins geraniin (1), corilagin (2), furosin (3), the flavonoids quercetin-3-O-beta-D-glucoside (isoquercitrin), kaempferol-3-O-beta-D-glucoside (astragalin), quercetin-3-O-D-rutinoside (rutin), gallic acid, methyl gallate, caffeic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid and caffeoylmalic acid (phaselic acid) have been identified in P. muellerianus for the first time. Geraniin was shown to be the dominant component of an aqueous extract.\n\nSuitable analytical methods for quality control of geraniin in P. muellerianus extract (methanol/water, 70/30) have been developed and validated based on ICH guidelines (ICH-compliant protocol).\n\nGeraniin and furosin increased the cellular energy status of human skin cells (dermal fibroblasts NHDF, HaCaT keratinocytes), triggering the cells towards higher proliferation rates, with fibroblasts being more sensitive than keratinocytes. Highest stimulation of NHDF by geraniin was found at 5 p,M, and of keratinocytes at 50-100 mu M. Furosin stimulated NHDF at about 50 mu M, keratinocytes at about 150-200 mu M.