Abstract
Previous studies have established that Ca2+-sensitive adenylyl cyclases, whether endogenously or heterologously expressed, are preferentially regulated by capacitative Ca2+ entry, compared with other means of elevating cytosolic Ca2+ (Chiono, M., Mahey, R., Tate, G., and Cooper, D. M. F. (1995) J. Biol. Chem. 270, 1149-1155; Fagan, K. A., Mahey, R., and Cooper, D. M. F. (1996) J. Biol. Chem. 271, 12438-12444; Fagan, K. A., Mons, N., and Cooper, D. M. F. (1998) J. Biol. Chem. 273, 9297-9305). These findings led to the suggestion that adenylyl cyclases and capacitative Ca2+ entry channels were localized in the same functional domain of the plasma membrane. In the present study, we have asked whether a heterologously expressed Ca2+-permeable channel could regulate the Ca2+-inhibitable adenylyl cyclase of C6-2B glioma cells. The cDNA coding for the rat olfactory cyclic nucleotide-gated channel was inserted into an adenovirus construct to achieve high levels of expression. Electrophysiological measurements confirmed the preservation of the properties of the expressed olfactory channel. Stimulation of the channel with cGMP analogs yielded a robust elevation in cytosolic Ca2+, which was associated with an inhibition of cAMP accumulation, comparable with that elicited by capacitative Ca2+ entry. These findings not only extend the means whereby Ca2+-sensitive adenylyl cyclases may be regulated, they also suggest that in tissues where they co-exist, cyclic nucleotide-gated channels and Ca2+-sensitive adenylyl cyclases may reciprocally modulate each other's activity.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.