Transient receptor potential ankyrin 1 channels are involved in spontaneous peptide hormone release from astrocytes

Astrocytes, a large population of glial cells, detect neurotransmitters and respond by increasing intracellular Ca²⁺ concentration ([Ca²⁺]_i) and releasing chemical molecules called gliotransmitters. Recently discovered Ca²⁺ influx through transient receptor potential ankyrin 1 (TRPA1) channels is reported to cause spontaneous [Ca²⁺]_i increase in astrocytes. While several physiological functions of TRPA1-mediated spontaneous Ca²⁺ signal have been revealed, relation with gliotransmitter release, especially peptide hormone exocytosis is largely unknown. We therefore explored the [Ca²⁺]_i and exocytosis dynamics in rat astrocyte cell line C6 cells and primary astrocytes. TRPA1-mediated spontaneous [Ca²⁺]_i transients were observed in both C6 cells and primary astrocytes. Total internal reflection fluorescence microscopy revealed that Venus-tagged brain-derived neurotrophic factor and neuropeptide Y were released spontaneously from astrocytes. Activation of TRPA1 channels enhanced the frequency of peptide hormone exocytosis, and inhibition of TRPA1 channels decreased the number of peptide hormone exocytosis. These results suggest that TRPA1-mediated spontaneous [Ca²⁺]_i increase modulates the spontaneous release of peptide hormones from astrocytes.