The effects of decreasing extracellular pH from 7.4 to 6.0 or 5.8 on whole cell membrane currents induced by GABA (10-100 //M) were studied in dorsal root ganglion (DRG) neurons of the frog in short-term culture using the whole cell patch-clamp technique. In 45 of 50 cells the GABA currents were the same at both normal and reduced pH. In the remaining 5 cells, acidification increased the response. The reversal potential for the current, about +5 mV, was the same at reduced and normal pH. These results contrast with the effect of the same pH reduction which markedly reduces the current resulting from glutamate activation of receptors on central neurons (Traynelis and Cull-Candy 1990, Vyklicky Jr. et ai 1990, Tang et al. 1990). These findings suggest that acidification under pathophysiological conditions plays a protective role in preventing excessive excitation not only by decreasing glutamate responses but also by leaving the inhibitory GABAa responses intact.
The effect of suramin, an inhibitor of G protein regulated signalling, was studied on the membrane currents induced by noxious heat and by capsaicin in cultured dorsal root ganglia neurones isolated from neonatal rats. Whole-cell responses induced by a heat ramp (24-52 °C) were little affected by suramin. The noxious heat-activated currents were synergistically facilitated in the presence of 0.3 µM capsaicin 13.2-fold and 6.3-fold at 40 °C and 50 °C, respectively. In 65% of neurones, the capsaicin-induced facilitation was inhibited by 10 µM suramin to 35±6 % and 53±6 % of control at 40 °C and 50 °C (S.E.M., n=15). Suramin 30 µM caused a significant increase in the membrane current produced by a nearly maximal dose (1 µM) of capsaicin over the whole recorded temperature range (2.4-fold at 25 °C and 1.2-fold at 48 °C). The results demonstrate that suramin differentially affects the interaction between capsaicin and noxious heat in DRG neurones and thus suggest that distinct transduction pathways may participate in vanilloid receptor activation mechanisms., V. Vlachová, A. Lyfenko, L. Vyklický, † R.K. Orkand., and Obsahuje bibliografii