Effect of menthol on cold receptor activity. Analysis of receptor processes

The effect of menthol on the discharge pattern of feline nasal and lingual cold receptors was analyzed in order to elucidate the underlying sensory transducer mechanism. A repetitive beating activity and burst (grouped) discharges were observed in both cold receptor populations at constant temperatures and after rapid cooling. An analysis of the impulse activity revealed a cyclic pattern of impulse generation, which suggested the existence of an underlying receptor potential oscillation that initiates impulses in the afferent nerve when it exceeds a threshold value. The frequency and amplitude of the periodic impulse-inducing receptor processes were characterized by the burst frequency, which increased with warming, and by the average number of impulses generated during each cycle, which increased with cooling. Menthol at micromolar concentrations induced an acceleration of the burst frequency at higher temperatures, but reduced the burst frequency in the midtemperature range. At temperatures above 25 degrees C, menthol increased the number of impulses elicited during each cycle and induced bursting in previously repetitively discharging fibers. At low temperatures, menthol suppressed bursting and finally inhibited all cold receptor activity. The impulse pattern at constant temperatures and during the dynamic response to rapid cooling was comparably affected by menthol. Calcium application completely abolished the stimulating menthol effect. Since, in equal concentrations, menthol specifically impairs neuronal calcium currents, the results are consistent with the conjecture that in cold receptors, menthol reduces the activation of a calcium-stimulated outward current by an impeding effect on a calcium conductance, thereby inducing depolarization and a modification of bursting behavior. The data confirm the hypothesis of a calcium-controlled outward conductance being involved in the generation of cyclic afferent activity in cold receptors.