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Abstract
Both trigeminal and spinal ganglion neurons show a strong potentiation of responses
to the irritant capsaicin in an acidic environment. The present study revealed that
there is also a strong interaction between protons and piperine, another vanilloid
irritant. We studied the mechanism of the interaction between protons and piperine.
Whole-cell patch clamp recordings were performed on cultured adult rat trigeminal
ganglion (TG) neurons voltage-clamped near their resting membrane potential (-60 mV).
Piperine (10 microM) caused a sustained net inward current associated with either
an increase or decrease in membrane conductance. When protons and piperine were co-applied,
the membrane currents evoked in piperine-sensitive TG neurons far exceeded the algebraic
sum of the responses to the two stimuli applied in isolation. Capsazepine blocked
the response of TG neurons to piperine at both physiological and acidic pH. In the
presence of capsazepine, responses to the mixture of piperine and protons resembled
the response to the low pH stimulus applied alone. Capsazepine had no effect on the
sustained proton-induced current. These findings suggest that protons enhance the
piperine current by altering the vanilloid receptor/channel complex or increasing
the length constant of the space clamp.