title: Role of RyRs and IP3 receptors after traumatic injury to spinal cord white matter.
abstract: Calcium influx and elevation of intracellular free calcium (Ca2+i), with subsequent activation of degenerative enzymes is hypothesized to cause cell injury and death after trauma. We examined the effects of traumatic compressive injury on (Ca2+)i dynamics in spinal cord white matter. We conducted electrophysiological studies with ryanodine and inositol (1,4,5)-triphosphate (IP3) receptor agonists and antagonists in an in vitro model of spinal cord injury (SCI). A 25-30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber (37 degrees C) and injured with a modified clip (2-g closing force) for 15 sec. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential (CAP) with glass microelectrodes. The CAP decreased to 55.2+/-6.8% of control (p < 0.05) after spinal cord injury (SCI). Chelation of Ca2+i with BAPTA-AM (a high-affinity calcium chelator) promoted significantly greater recovery of CAP amplitude (83.2+/-4.2% of control; p < 0.05) after injury. Infusion of caffeine (1 and 10 mM) exacerbated CAP amplitude decline (45.1+/-5.9% of control; p < 0.05; 44.6+/-3.1% of control; p < 0.05) postinjury. Blockade of Ca2+i release through ryanodine-sensitive receptors (RyRs) with dantrolene (10 microM) and ryanodine (50 microM), conferred significant (p < 0.05) improvement in CAP amplitude after injury. On the other hand, blockade of Ca2+i with inositol (1,4,5)-triphosphate receptor (IP3Rs) blocker 2APB (10 microM) also conferred significant improvement in CAP amplitude after injury (82.9+/-7.9%; p < 0.05). In conclusion, the injurious effects of Ca2+i in traumatic central nervous system (CNS) white matter injury appear to be mediated both by RyRs and through IP3Rs calcium-induced calcium release receptors (CICRs).
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha 68198-2035, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Thorell
authors.forename: L G
authors.initials: LG
authors.lastname: Leibrock
authors.forename: S K
authors.initials: SK
authors.lastname: Agrawal
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004594:Electrophysiology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D023421:Models, Animal; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012433:Ryanodine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D001896:Boron Compounds; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000697:Central Nervous System Stimulants; D002614:Chelating Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009125:Muscle Relaxants, Central; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; C109986:2-aminoethoxydiphenyl borate; D003620:Dantrolene; D002118:Calcium