Extracellular protons both increase the activity and reduce the conductance of capsaicin- gated channels.

Capsaicin evokes a membrane current in trigeminal ganglion neurons that is increased substantially in a moderately acidic extracellular environment. Using excised outside-out membrane patches, we studied the mechanism by which protons enhance the sustained response to capsaicin. In the absence of capsaicin, extracellular exposure to a moderately acidic physiological solution (pH 6.6) did not result in sustained channel openings in any capsaicin-sensitive outside-out patches. When co-applied with capsaicin, the acidic extracellular solution greatly increased the probability of capsaicin-gated channels being in the open state. In addition, acidic extracellular solution appeared to increase the number of channels available to be opened by capsaicin. The amplitude of the unitary currents was reduced by the acidic extracellular solution. These results show that the proton enhancement of the capsaicin-evoked whole-cell excitatory current is attributable to proton-receptive site(s) causing a marked increase in the activity of capsaicin-gated channels.