title: 1alpha,25-dihydroxy-vitamin-D3-induced store-operated Ca2+ influx in skeletal muscle cells. Modulation by phospholipase c, protein kinase c, and tyrosine kinases.
abstract: In skeletal muscle cells the steroid hormone 1alpha, 25-dihydroxy-vitamin-D3 (1,25(OH)2D3) nongenomically promotes Ca2+ release from intracellular stores and cation influx through both L-type and store-operated Ca2+ (SOC) channels. In the present work we evaluated the regulation and kinetics of the 1, 25(OH)2D3-stimulated SOC influx in chick muscle cells. Stimulation with 10(-9) M 1,25(OH)2D3 in Ca2+-free medium resulted in a rapid (40-60 s) but transient [Ca2+]i rise, which correlated with sterol-dependent inositol 1,4,5-trisphosphate production. The SOC influx stimulated by the hormone was insensitive to both L-type channel antagonists and polyphosphoinositide-specific phospholipase C (PPI-PLC) inhibitors but was fully inhibitable by La3+ and Ni2+. PPI-PLC blockade prior to 1,25(OH)2D3 stimulation suppressed both the [Ca2+]i transient and the SOC influx. 1,25(OH)2D3-induced SOC entry was markedly increased after 3 min of treatment (30% above basal) and then rapidly reached a steady-state level. The sterol-stimulated SOC influx was prevented by protein kinase C and tyrosine kinase inhibitors but unaffected by blockade of the protein kinase A pathway. None of these inhibitors altered the thapsigargin-induced SOC entry, suggesting the operation of a signaling mechanism different from that for sterol-dependent SOC influx. The present results indicate that 1,25(OH)2D3-induced activation of PPI-PLC is upstream to Ca2+ influx through SOC channels and point for a role of both protein kinase C and tyrosine kinases but not protein kinase A in the regulation of the sterol-dependent SOCE pathway.
authors.affiliation: Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, (8000) Bahía Blanca, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Vazquez
authors.forename: A R
authors.initials: AR
authors.lastname: de Boland
authors.forename: R L
authors.initials: RL
authors.lastname: Boland
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D008345:Manganese / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D008345:Manganese; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D014700:Verapamil; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002117:Calcitriol; D009355:Neomycin; D009543:Nifedipine; D002118:Calcium