title: Regulation of a Ca2+-sensitive adenylyl cyclase in an excitable cell. Role of voltage-gated versus capacitative Ca2+ entry.
abstract: In nonexcitable cells, we had previously established that Ca(2+)-sensitive adenylyl cyclases, whether expressed endogenously or heterologously, were regulated exclusively by capacitative Ca(2+) entry (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). Relatively little is known about how these enzymes are regulated by Ca(2+) in excitable cells, where they predominate. Furthermore, no effort has been made to determine whether the prominent voltage-gated Ca(2+) entry, which typifies excitable cells, overwhelms the effect of any capacitative Ca(2+) entry that may occur. In the present study, we placed the Ca(2+)-stimulable, adenylyl cyclase type VIII in an adenovirus vector to optimize its expression in the pituitary-derived GH(4)C(1) cell line. In these cells, a modest degree of capacitative Ca(2+) entry could be discerned in the face of a dramatic voltage-gated Ca(2+) entry. Nevertheless, both modes of Ca(2+) entry were equally efficacious at stimulating adenylyl cyclase. A striking release of Ca(2+) from intracellular stores, triggered either by ionophore or thyrotrophin-releasing hormone, was incapable of stimulating the adenylyl cyclase. It thus appears as though the intimate colocalization of adenylyl cyclase with capacitative Ca(2+) entry channels is an intrinsic property of these molecules, regardless of whether they are expressed in excitable or nonexcitable cells.
authors.affiliation: Departments of Pharmacology and Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Fagan
authors.forename: R A
authors.initials: RA
authors.lastname: Graf
authors.forename: S
authors.initials: S
authors.lastname: Tolman
authors.forename: J
authors.initials: J
authors.lastname: Schaack
authors.forename: D M
authors.initials: DM
authors.lastname: Cooper
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating; D051381:Rats
chemical_list: D000262:Adenylyl Cyclases; D002118:Calcium