title: Changes in gap junction expression and function following ischemic injury of spinal cord white matter.
abstract: Gap junctions are widely present in spinal cord white matter; however, their role in modulating the dynamics of axonal dysfunction remains largely unexplored. We hypothesized that inhibition of gap junctions reduces the loss of axonal function during oxygen and glucose deprivation (OGD). The functional role of gap junctions was assessed by electrophysiological recordings of compound action potentials (CAPs) in Wistar rat spinal cord slices with the sucrose gap technique. The in vitro slices were subjected to 30-min OGD. Gap junction connexin (Cx) mRNA expression was determined by qPCR and normalized to β-actin. A 30-min OGD resulted in reduction of CAPs to 14.8 ± 4.6% of their pre-OGD amplitude (n = 5). In the presence of gap junction blockers carbenoxolone (Cbx; 100 μM) and 1-octanol (Oct; 300 μM), the CAP reduction in OGD was to only 35.7 ± 5.7% of pre-OGD amplitude in Cbx (n = 9) and to 37.4 ± 8.9% of pre-OGD amplitude in Oct (n = 10). Both drugs also noticeably prolonged the half-decline time of CAP amplitudes in OGD from 6.0 min in no-drug conditions to 9.6 min in the presence of Cbx and to 7.7 min in the presence of Oct, suggesting that blocking gap junctions reduces conduction loss during OGD. With application of Cbx and Oct in the setting of OGD, expression of Cx30 and Cx43 mRNA was downregulated. Our data provide new insights into the role of gap junctions in white matter ischemia and reveal the necessity of a cautious approach in determining detrimental or beneficial effects of gap junction blockade in white matter ischemia.
authors: Division of Neurosurgery and Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada; Departments of Physiology and.
authors: Karina
authors: K
authors: Goncharenko
authors: Division of Neurosurgery and Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada;
authors: Eftekhar
authors: E
authors: Eftekharpour
authors: Division of Neurosurgery and Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada; Departments of Physiology and Surgery, University of Toronto, Toronto, Ontario, Canada.
authors: Alexander A
authors: AA
authors: Velumian
authors: Division of Neurosurgery and Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada; Departments of Physiology and.
authors: Peter L
authors: PL
authors: Carlen
authors: Division of Neurosurgery and Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada; Surgery, University of Toronto, Toronto, Ontario, Canada michael.fehlings@uhn.ca.
authors: Michael G
authors: MG
authors: Fehlings
mesh_terms: D020003:1-Octanol / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D015687:Cell Hypoxia; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000378:metabolism*; D066127:White Matter / Q000378:metabolism* / Q000502:physiology
chemical_list: D017630:Connexins; D012333:RNA, Messenger; D005947:Glucose; D002229:Carbenoxolone; D020003:1-Octanol
keywords: connexins; electrophysiology; gap junctions; oxygen-glucose deprivation; spinal cord injury