Fagan, KA; Rich, TC; Tolman, S; Schaack, J; Karpen, JW; Cooper, DMF

Journal of Biological Chemistry [J. Biol. Chem.], vol. 274, no. 18, pp. 12445-12453, 30 Apr 1999

Previous studies have established that Ca super(2+)-sensitive adenylyl cyclases, whether endogenously or heterologously expressed, are preferentially regulated by capacitative Ca super(2+) entry, compared with other means of elevating cytosolic Ca super(2+). These findings led to the suggestion that adenylyl cyclases and capacitative Ca super(2+) entry channels were localized in the same functional domain of the plasma membrane. In the present study, we have asked whether a heterologously expressed Ca super(2+)-permeable channel could regulate the Ca super(2+)-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 Ca super(2+), which was associated with an inhibition of cAMP accumulation, comparable with that elicited by capacitative Ca super(2+) entry. These findings not only extend the means whereby Ca super(2+)-sensitive adenylyl cyclases may be regulated, they also suggest that in tissues where they co-exist cyclic nucleotide-gated channels and Ca super(2+)-sensitive adenylyl cyclases may reciprocally modulate each other's activity.