A ryanodine receptor-like Ca2+ channel is expressed in nonexcitable cells.
In this study we investigated the effects of 4-chloro-3-ethylphenol on Ca2+ homeostasis, and we report that this compound induces Ca2+ release from a ruthenium red-sensitive Ca2+ release channel present in skeletal muscle terminal cisternae. When tested with bovine cerebellar microsomes, the Ca(2+)-releasing activity of 4-chloro-3-ethylphenol was reduced by ruthenium red and unaffected by heparin. In PC-12 cells, HL-60 cells, human fibroblasts, the human hepatoma cell line PLC/PRF/5, and Jurkat cells, 4-chloro-3-ethylphenol released Ca2+ from intracellular thapsigargin-sensitive stores. Although decreased, its effect was retained after treatment of intact/permeabilized cells with inositol-1,4,5-trisphosphate (IP3)-mobilizing agonists/IP3, whereas pretreatment of permeabilized cells with ruthenium red reduced the Ca(2+)-releasing activity of 4-chloro-3-ethylphenol. These results provide functional evidence for the presence of a Ca2+ channel distinct from the IP3 receptor, having pharmacological similarities to the ryanodine receptor, in the intracellular Ca2+ stores of a variety of nonexcitable cells. We also demonstrate that a monoclonal anti-ryanodine receptor antibody recognizes a protein in human fibroblasts with similar apparent molecular mass the ryanodine receptor. Thus, the intracellular Ca2+ stores of mammalian cells appear to be endowed with two distinct intracellular Ca2+ channels.
Larini
F
F
Institute of General Pathology, University of Ferrara, Italy.
Menegazzi
P
P
Baricordi
O
O
Zorzato
F
F
Treves
S
S
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002463:Cell Membrane Permeability; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D002733:Chlorophenols / Q000494:pharmacology; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D016716:PC12 Cells; D011817:Rabbits; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D002733:Chlorophenols; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D013729:Terpenes; D012430:Ruthenium Red; C091710:4-chloro-3-ethylphenol; D019284:Thapsigargin; D002118:Calcium