Oscillatory Current Responses of Olfactory Receptor Neurons to Odorants and Computer Simulation Based on a Cyclic AMP Transduction Model

摘要

Neural oscillatory activities triggered by odorant stimulation have been often reported at various of olfactory nervous systems in vertebrates. To elucidate the origin of neural oscillations, we studied first the oscillatory properties of current responses of isolated olfactory receptor neurons (ORNs) of the rainbow trout to amino acid odorants, using a whole-cell voltage-clamp technique and found that the damped current oscillations were intrinsic in both ciliated and microvillous ORNs and occurred when ORNs were stimulated by odorants at high intensities. COntinuous wavelet analysis usint the Gabor function revealed that the dominant frequency of oscillations was 1.89 +- 0.50 Hz (mean +- SD, n = 92). There was no significant difference in oscillation frequency between the two types of ORNs and between different perfusion conditions with standard and Na~+-free (choline) Ringer's solutions, but there was a slight difference in oscillation frequency between different holding potential conditions of negative and positive potentials. We then performed a computer simulation of the current responses with a cAMP olfactory transduction model. The model was based on the assumption that the current responses of ORNs were linearly related to the sum of concentrations of active cyclic-nucleotide-gated channels and Ca~(2+)-activated Cl~- channels, and was expressed by 12 differential equations with 44 different parameters. The simulation revealed that the oscillations of current responses of ORNs were mainly due to the oscillatory properties of intracellular cAMP and Ca~(2+) concentrations. The necessary reaction component for the oscillations in the transduction model was direct inhibition of adenylate cyclase activity by Ca~(2+). High Ca~(2+) efflux by the Na~+-Ca~(2+) exchanger and cAMP-phosphodiesterase activity were most influential on the oscillations. The simulation completely represented the characteristics of current responses of ORNs: odorant-intensity-dependent response, intensity-dependent latency and adaptation. Thus, the simulation is generally applicable to current and voltage responses of ORNs equipped with cAMP olfactory transduction pathway in other vertebrate species. The simulation programs for Macintosn (cAMP9.2.7 and 9.2.8 for MacOS 8.1 or later) and cAMP JAVA applet versions based on cAMP 9.2.8 have been published on the world wide web .