title: Fatty acyl-CoA-acyl-CoA-binding protein complexes activate the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum.
abstract: We previously reported that fatty acyl-CoA esters activate ryanodine receptor/Ca2+ release channels in a terminal cisternae fraction from rabbit skeletal muscle [Fulceri, Nori, Gamberucci, Volpe, Giunti and Benedetti (1994) Cell Calcium 15, 109-116]. Skeletal muscle cytosol contains a high-affinity fatty acyl-CoA-binding protein (ACBP) [Knudsen, Hojrup, Hansen, H.O., Hansen, H.F. and Roepstorff (1989) Biochem. J. 262, 513-519]. We show here that palmitoyl-CoA (PCoA) in a complex with a molar excess of bovine ACBP causes a discrete Ca2+ efflux or allows Ca2+ release from the Ca2+-preloaded terminal cisternae fraction by sub-optimal caffeine concentrations. Both effects were abolished by elevating the free [Mg2+] in the system, which inhibits the Ca2+ release channel activity. Sensitization towards caffeine was a function of both the concentration of the complex and the [PCoA]-to-[ACBP] ratio. In all experimental conditions the calculated free [PCoA] was no more than 50 nM, and such concentrations by themselves were inactive on Ca2+ release channels. The KD for PCoA binding was approx. 2 nM for bovine and yeast ACBP, and slightly higher (8 nM) for rat ACBP. The PCoA-rat ACBP complex behaved in the same manner as the PCoA-bovine ACBP complex, whereas the ester complexed with yeast ACBP was more active in activating/sensitizing Ca2+ efflux. A non-hydrolysable analogue of PCoA bound to (bovine) ACBP also sensitized the Ca2+ release channel towards caffeine. These findings indicate that fatty acyl-CoA-ACBP complexes either interact directly with one or more components in the terminal cisternae membranes or, through interaction with the component(s), donate the fatty acyl-CoA esters to high-affinity binding sites of the membrane, thus affecting (and possibly regulating) Ca2+ release channel activity.
authors.affiliation: Istituto di Patologia Generale, Viale A. Moro, Università di Siena, 53100 Siena, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Fulceri
authors.forename: J
authors.initials: J
authors.lastname: Knudsen
authors.forename: R
authors.initials: R
authors.lastname: Giunti
authors.forename: P
authors.initials: P
authors.lastname: Volpe
authors.forename: A
authors.initials: A
authors.lastname: Nori
authors.forename: A
authors.initials: A
authors.lastname: Benedetti
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D003065:Coenzyme A / Q000494:pharmacology; D026261:Diazepam Binding Inhibitor; D005456:Fluorescent Dyes / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010171:Palmitoyl Coenzyme A / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014966:Xanthenes / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D000814:Aniline Compounds; D015220:Calcium Channels; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D005456:Fluorescent Dyes; D005656:Fungal Proteins; D009124:Muscle Proteins; D011994:Recombinant Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D014966:Xanthenes; D010171:Palmitoyl Coenzyme A; C059715:Fluo-3; D002110:Caffeine; C032421:heptadecan-2-onyl-dethio-coenzyme A; D008274:Magnesium; D003065:Coenzyme A; D002118:Calcium