Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal cord white matter injury

S. K. Agrawal, R. Nashmi, M. G. Fehlings

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Recent work has suggested a potential role for voltage-gated Ca2+ channels in the pathophysiology of anoxic central nervous system white matter injury. To examine the relevance of these findings to neurotrauma, we conducted electrophysiological studies with inorganic Ca2+ channels blockers and L- and N-subtype-specific calcium channel antagonists in an in vitro model of spinal cord injury. Confocal immunohistochemistry was used to examine for localization of L- and N-type calcium channels in spinal cord white matter tracts. A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber and injured with a modified clip (2g closing force) for 15s. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential at two points with glass microelectrodes. The compound action potential decreased to 71.4±2.0% of control (P<0.05) after spinal cord injury. Removal of extracellular Ca2+ promoted significantly greater recovery of compound action potential amplitude (86.3±7.6% of control; P< 0.05) after injury. Partial blockade of voltage-gated Ca2+ channels with cobalt (20μM) or cadmium (200μM) conferred improvement in compound action potential amplitude. Application of the L-type Ca2+ channel blockers diltiazem (50μM) or verapamil (90μM), and the N-type antagonist ω-conotoxin GVIA (1μM), significantly enhanced the recovery of compound action potential amplitude postinjury. Co-application of the L-type antagonist diltiazem with the N-type blocker ω-conotoxin GVIA showed significantly greater (P<0.05) improvement in compound action potential amplitude than application of either drug alone. Confocal immunohistochemistry with double labelling for glial fibrillary acidic protein, GalC and NF200 demonstrated L- and N-type Ca2+ channels on astrocytes and oligodendrocytes, but not axons, in spinal cord white matter.In conclusion, the injurious effects of Ca2+ in traumatic central nervous system white matter injury appear to be partially mediated by voltage-gated Ca2+ channels. The presence of L- and N-type Ca2+ channels on periaxonal astrocytes and oligodendrocytes suggests a role for these cells in post-traumatic axonal conduction failure. Copyright (C) 2000 IBRO.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalNeuroscience
Volume99
Issue number1
DOIs
StatePublished - Jul 26 2000

Fingerprint

N-Type Calcium Channels
L-Type Calcium Channels
Action Potentials
Spinal Cord
Wounds and Injuries
Conotoxins
Diltiazem
Oligodendroglia
Spinal Cord Injuries
Astrocytes
Central Nervous System
Immunohistochemistry
Glial Fibrillary Acidic Protein
Calcium Channel Blockers
Microelectrodes
Verapamil
Cobalt
Cadmium
Surgical Instruments
Glass

Keywords

  • Astrocytes
  • Calcium channels
  • Conotoxin
  • Glia
  • Oligodendrocytes
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal cord white matter injury. / Agrawal, S. K.; Nashmi, R.; Fehlings, M. G.

In: Neuroscience, Vol. 99, No. 1, 26.07.2000, p. 179-188.

Research output: Contribution to journalArticle

@article{28c241d7cc44450da38a12c096a7e0d2,
title = "Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal cord white matter injury",
abstract = "Recent work has suggested a potential role for voltage-gated Ca2+ channels in the pathophysiology of anoxic central nervous system white matter injury. To examine the relevance of these findings to neurotrauma, we conducted electrophysiological studies with inorganic Ca2+ channels blockers and L- and N-subtype-specific calcium channel antagonists in an in vitro model of spinal cord injury. Confocal immunohistochemistry was used to examine for localization of L- and N-type calcium channels in spinal cord white matter tracts. A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber and injured with a modified clip (2g closing force) for 15s. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential at two points with glass microelectrodes. The compound action potential decreased to 71.4±2.0{\%} of control (P<0.05) after spinal cord injury. Removal of extracellular Ca2+ promoted significantly greater recovery of compound action potential amplitude (86.3±7.6{\%} of control; P< 0.05) after injury. Partial blockade of voltage-gated Ca2+ channels with cobalt (20μM) or cadmium (200μM) conferred improvement in compound action potential amplitude. Application of the L-type Ca2+ channel blockers diltiazem (50μM) or verapamil (90μM), and the N-type antagonist ω-conotoxin GVIA (1μM), significantly enhanced the recovery of compound action potential amplitude postinjury. Co-application of the L-type antagonist diltiazem with the N-type blocker ω-conotoxin GVIA showed significantly greater (P<0.05) improvement in compound action potential amplitude than application of either drug alone. Confocal immunohistochemistry with double labelling for glial fibrillary acidic protein, GalC and NF200 demonstrated L- and N-type Ca2+ channels on astrocytes and oligodendrocytes, but not axons, in spinal cord white matter.In conclusion, the injurious effects of Ca2+ in traumatic central nervous system white matter injury appear to be partially mediated by voltage-gated Ca2+ channels. The presence of L- and N-type Ca2+ channels on periaxonal astrocytes and oligodendrocytes suggests a role for these cells in post-traumatic axonal conduction failure. Copyright (C) 2000 IBRO.",
keywords = "Astrocytes, Calcium channels, Conotoxin, Glia, Oligodendrocytes, Rat",
author = "Agrawal, {S. K.} and R. Nashmi and Fehlings, {M. G.}",
year = "2000",
month = "7",
day = "26",
doi = "10.1016/S0306-4522(00)00165-2",
language = "English (US)",
volume = "99",
pages = "179--188",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal cord white matter injury

AU - Agrawal, S. K.

AU - Nashmi, R.

AU - Fehlings, M. G.

PY - 2000/7/26

Y1 - 2000/7/26

N2 - Recent work has suggested a potential role for voltage-gated Ca2+ channels in the pathophysiology of anoxic central nervous system white matter injury. To examine the relevance of these findings to neurotrauma, we conducted electrophysiological studies with inorganic Ca2+ channels blockers and L- and N-subtype-specific calcium channel antagonists in an in vitro model of spinal cord injury. Confocal immunohistochemistry was used to examine for localization of L- and N-type calcium channels in spinal cord white matter tracts. A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber and injured with a modified clip (2g closing force) for 15s. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential at two points with glass microelectrodes. The compound action potential decreased to 71.4±2.0% of control (P<0.05) after spinal cord injury. Removal of extracellular Ca2+ promoted significantly greater recovery of compound action potential amplitude (86.3±7.6% of control; P< 0.05) after injury. Partial blockade of voltage-gated Ca2+ channels with cobalt (20μM) or cadmium (200μM) conferred improvement in compound action potential amplitude. Application of the L-type Ca2+ channel blockers diltiazem (50μM) or verapamil (90μM), and the N-type antagonist ω-conotoxin GVIA (1μM), significantly enhanced the recovery of compound action potential amplitude postinjury. Co-application of the L-type antagonist diltiazem with the N-type blocker ω-conotoxin GVIA showed significantly greater (P<0.05) improvement in compound action potential amplitude than application of either drug alone. Confocal immunohistochemistry with double labelling for glial fibrillary acidic protein, GalC and NF200 demonstrated L- and N-type Ca2+ channels on astrocytes and oligodendrocytes, but not axons, in spinal cord white matter.In conclusion, the injurious effects of Ca2+ in traumatic central nervous system white matter injury appear to be partially mediated by voltage-gated Ca2+ channels. The presence of L- and N-type Ca2+ channels on periaxonal astrocytes and oligodendrocytes suggests a role for these cells in post-traumatic axonal conduction failure. Copyright (C) 2000 IBRO.

AB - Recent work has suggested a potential role for voltage-gated Ca2+ channels in the pathophysiology of anoxic central nervous system white matter injury. To examine the relevance of these findings to neurotrauma, we conducted electrophysiological studies with inorganic Ca2+ channels blockers and L- and N-subtype-specific calcium channel antagonists in an in vitro model of spinal cord injury. Confocal immunohistochemistry was used to examine for localization of L- and N-type calcium channels in spinal cord white matter tracts. A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber and injured with a modified clip (2g closing force) for 15s. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential at two points with glass microelectrodes. The compound action potential decreased to 71.4±2.0% of control (P<0.05) after spinal cord injury. Removal of extracellular Ca2+ promoted significantly greater recovery of compound action potential amplitude (86.3±7.6% of control; P< 0.05) after injury. Partial blockade of voltage-gated Ca2+ channels with cobalt (20μM) or cadmium (200μM) conferred improvement in compound action potential amplitude. Application of the L-type Ca2+ channel blockers diltiazem (50μM) or verapamil (90μM), and the N-type antagonist ω-conotoxin GVIA (1μM), significantly enhanced the recovery of compound action potential amplitude postinjury. Co-application of the L-type antagonist diltiazem with the N-type blocker ω-conotoxin GVIA showed significantly greater (P<0.05) improvement in compound action potential amplitude than application of either drug alone. Confocal immunohistochemistry with double labelling for glial fibrillary acidic protein, GalC and NF200 demonstrated L- and N-type Ca2+ channels on astrocytes and oligodendrocytes, but not axons, in spinal cord white matter.In conclusion, the injurious effects of Ca2+ in traumatic central nervous system white matter injury appear to be partially mediated by voltage-gated Ca2+ channels. The presence of L- and N-type Ca2+ channels on periaxonal astrocytes and oligodendrocytes suggests a role for these cells in post-traumatic axonal conduction failure. Copyright (C) 2000 IBRO.

KW - Astrocytes

KW - Calcium channels

KW - Conotoxin

KW - Glia

KW - Oligodendrocytes

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=0034718228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034718228&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(00)00165-2

DO - 10.1016/S0306-4522(00)00165-2

M3 - Article

C2 - 10924962

AN - SCOPUS:0034718228

VL - 99

SP - 179

EP - 188

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 1

ER -