title: Adenosine(5')hexaphospho(5')adenosine stimulation of a Ca(2+)-induced Ca(2+)-release channel from skeletal muscle sarcoplasmic reticulum.
abstract: Stimulation of a Ca(2+)-induced Ca(2+)-release channel from skeletal muscle sarcoplasmic reticulum by various adenosine(5')oligophospho(5')adenosines (ApnA, n = 2-6) by a rapid quenching technique using radioactive calcium was studied. Ap4A, Ap5A and Ap6A, as well as adenosine 5'-[beta, gamma-methylene]triphosphate (AdoPP [CH2]P), a non-hydrolyzable ATP analogue, stimulated the Ca(2+)-release channel, whereas Ap2A and Ap3A had no effect. At a concentration of 0.5 mM, the order of stimulation was AdoPP[CH2]P less than Ap4A less than Ap5A much less than Ap6A. As well as having the highest affinity (0.44 mM for half-maximal stimulation), Ap6A showed an extraordinarily high Hill coefficient of 3.3 (1.9 for AdoPP[CH2]P, 2.1 for Ap5A). The stimulating effect of Ap6A was reversible, yet its dissociation proceeded very slowly. Stimulation of Ca2+ release by Ap6A was counteracted by Mg2+ and ruthenium red. A 2',3'-dialdehyde derivative of Ap6A, which is a chemical probe for amino groups, stimulated irreversibly the Ca(2+)-release channel and modified some high-molecular-mass sarcoplasmic reticulum proteins, possibly including the channel protein. Our data suggest that Ap6A stimulates the Ca2+ channel by binding to the activation site of the channel subunit and simultaneously preventing the spontaneous decay of the Ca2+ channel by keeping together two of the four channel subunits by bridging them with its two adenosine groups.
authors.affiliation: Max-Planck-Institute for Medical Research, Heidelberg, Federal Republic of Germany.
authors.forename: H
authors.initials: H
authors.lastname: Morii
authors.forename: M
authors.initials: M
authors.lastname: Makinose
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002413:Cations, Divalent; D015226:Dinucleoside Phosphates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D008274:Magnesium / Q000494:pharmacology; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D012430:Ruthenium Red / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002413:Cations, Divalent; D015226:Dinucleoside Phosphates; D012430:Ruthenium Red; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D008274:Magnesium; D002118:Calcium