Fig. 8.

Sustained potentiation of carbachol-evoked Ca²⁺ signals is mediated by cAMP junctions. (A) Effects of SQ/DDA and IBMX (concentrations as in Fig. 7C) on the increase in intracellular cAMP concentration evoked by NKH477 (300 µM, 15 min). (B,C) Effects of the same treatments on the peak Ca²⁺ signals evoked by carbachol (20 µM) after incubation for 15 min with the indicated concentrations of NKH477. (D,E) Similar analyses of the effects of SQ/DDA and/or IBMX on the increase in intracellular cAMP concentration evoked by incubation with the indicated concentrations of PTH(1-34) for 60 min (D) or the peak Ca²⁺ signals evoked by carbachol (20 µM) added 60 min after PTH(1-34) (E). Results in A–E are mean±s.e.m., n = 3. (F) Relationships between cAMP and Δ[Ca²⁺]_c for cells stimulated with PTH(1-34) for 60 min alone or after treatment with SQ/DDA or IBMX (mean±s.e.m., n = 3). (G) Normally cAMP is delivered to IP₃R within signalling junctions (left panel), but the massive accumulation of cAMP during sustained stimulation with PTH and IBMX (right panel) achieves global cytosolic cAMP concentrations sufficient to sensitize IP₃Rs beyond active junctions. (H) Targets of the drugs used. AC, adenylyl cyclase.