Porphyrin induced calcium release from skeletal muscle sarcoplasmic reticulum.
Micromolar concentrations of the porphyrin mesotetra(4-N-methylpyridyl)porphine tetraiodide is shown to induce rapid release of Ca2+ from skeletal muscle sarcoplasmic reticulum vesicles. Porphyrin-induced Ca2+ release is stimulated by ATP (KdATP = 100 microM) and Ca2+ (KdCa = 1 microM) and is inhibited by Mg2+ (KI = 220 microM) and ruthenium red (KI = 7 nM). The porphyrin is also shown to stimulate high affinity [3H]ryanodine binding by decreasing the dissociation constant (kd) and increasing the binding capacity (Bmax). Moreover, in the presence of Mg2+, receptor binding is sensitized to activation by Ca2+, and porphyrin-stimulated channel activity is sensitized to activation by Ca2+. These observations show that porphyrin-induced Ca2+ release is due to a direct interaction with the Ca2+ release protein from sarcoplasmic reticulum.
Abramson
J J
JJ
Department of Physics, Portland State University, Oregon 97207.
Milne
S
S
Buck
E
E
Pessah
I N
IN
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008652:Mesoporphyrins / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D011817:Rabbits; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D008652:Mesoporphyrins; D011166:Porphyrins; D012430:Ruthenium Red; D012433:Ryanodine; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C021096:tetra(4-N-methylpyridyl)porphine; D002110:Caffeine; D000255:Adenosine Triphosphate; D008274:Magnesium; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D004229:Dithiothreitol