Involvement of the calcium channel beta3 subunit in olfactory signal transduction.

Despite the expression of voltage-dependent Ca2+ channels in nasal turbinate epithelium, their role in odorant chemosensation has remained obscure. Therefore, we investigated olfactory neurotransduction in beta3-deficient mice. RT-PCR and Western blots confirmed the expression of various types of Ca2+ channels in the nasal turbinate. Electrophysiological evaluations revealed that beta3-null mice had a 60% reduction in the high-voltage-dependent Ca2+ currents in olfactory receptor neurons due to reduced N- and L-type channel currents. The beta3-null mice showed increased olfactory neuronal activity to triethylamine, and this effect was mimicked by the perfusion of the specific N-type Ca2+ channel inhibitor omega-conotoxin GVIA in the electro-olfactogram. Diluted male urine odors induced higher Fos immunoreactivity in the main olfactory bulbs of beta3-deficient mice, indicating enhanced signal transduction of odor information in these mice. Our data indicate the involvement of voltage-dependent Ca2+ channels and importance of the beta3 subunit in olfactory signal transduction.

Decreases in urinary pheromonal activities in male mice after exposure to 3-methylchoranthrene.

Many classes of environmental pollutants, which are found at significant levels in the environment, affect the reproductive functions. The gonadal functions of various animals are regulated by pheromones excreted from mating partners. Pheromones in male urine play essential roles in the sexual maturation of female mice. Pheromones are received by sensory neurons in the vomeronasal organ, which innervate to the accessory olfactory bulb (AOB). The effects of a typical aromatic environmental pollutant (3-methylchoranthrene) on excretion of pheromones from male mice were explored based on neuronal Fos responses of the AOB of female mice. On days 1 and 3 after intraperitoneal administration of 3-methylchoranthrene (3-MC), the density of Fos-immunoreactive (Fos-ir) cells in the AOB of female mice after exposure to urine excreted from the administered males was lower than that after exposure to urine from non-administered males. These results suggest that 3-MC blocks chemical communication from male to female mice by reducing pheromonal activities.

Decreases in pheromonal responses at the accessory olfactory bulb of mice with a deficiency of the alpha1B or beta3 subunits of voltage-dependent Ca2+-channels.

Pheromones affect gonadal functions and sexual behaviors. Information in regard to pheromones is received by the vomeronasal organ (VNO) and transmitted to the accessory olfactory bulb (AOB). We investigated the physiological role of the alpha1B and beta3 subunits of the N (neuronal)-type voltage-dependent Ca2+ channel in the neurotransduction in the accessory olfactory (vomeronasal) system using alpha1B-deficient mice and beta3-deficient mice. RT-PCR studies showed the existence of beta1, beta2, beta3, beta4, alpha1A, alpha1B, and alpha1C subunits of voltage-dependent Ca2+ channels in the mouse VNO. Immunohistochemical studies showed that the alpha1A, alpha1B, and alpha1C subunits of voltage-dependent Ca2+ channels exist in the sensory neurons and supporting cells of the mouse VNO. Exposure of the VNO to urine samples excreted from male mice induced lower Fos-immunoreactivity in the periglomerular (PG) cells of the AOBs in alpha1B-deficient female mice than in those of wild mice. The density of Fos-immunoreactive (Fos-ir) cells after exposure to female urine samples at the periglomerular cell layer of alpha1B-deficient male mice was lower than that of wild mice. Exposure of the VNO of beta3-deficient female mice to male urine samples also induced low Fos-ir cells in the periglomerular cell layer of the AOB. These data suggest the importance of the alpha1B and beta3 subunits of the N-type voltage-dependent Ca2+ channel for the pheromone signal transduction system.