Membrane currents induced by capsaicin (CAPS) in cultured sensory neurons from 1- to 2-day-old rats were studied. Responses to CAPS (lO^M) exceeding 1 nA at -50 mV were found in smaller, usually bipolar or tripolar neurons in which GABA (30 yuM) induced small or no response. Large, unipolar neurons, which exhibited large responses to GABA, were completely insensitive to CAPS (10//M). In contrast to GABA, responses to CAPS exhibited a slow rise and slow decay and a marked tachyphylaxis after repeated CAPS applications at high concentrations which made it difficult to study the concentration-response relationship. In partially run-down neurons, which exhibited quasi stable responses, the slope of the ascending phase was concentration-dependent with an apparent association rate constant Ki 9x104 [M-1s-1]. The time constant of the decay was 3.5 s, and was concentration-independent. However, in 5 neurones the EC50 measured from the first series of CAPS applications at increasing concentrations was 0.31 ±0.5ptA with a Hill coefficient 1.66±0.35. The responses to CAPS reversed at +10.4±2.5 mV suggesting that the current is carried nonselectively by monovalent cations and Ca2+. The channel conductance of CAPS-gated channels at -50 mV calculated from the mean membrane current and variance of the current noise in outside-out patches or measured directly was 28 pS (n=5). It is suggested that the CAPS-gated channels are either controlled by receptors with a very high affinity or that the channels are controlled by membrane-bound protein(s) which do not depend in their function on the supply of GTP or other intracellular metabolites.
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.