The critical role of voltage-dependent calcium channel in axonal repair following mechanical trauma.
Membrane disruption following mechanical injury likely plays a critical role in the pathology of spinal cord trauma. It is known that intracellular calcium is a key factor that is essential to membrane resealing. However, the differential role of calcium influx through the injury site and through voltage dependent calcium channels (VDCC) has not been examined in detail. Using a well-established ex vivo guinea-pig spinal cord white matter preparation, we have found that axonal membrane resealing was significantly inhibited following transection or compression in the presence of cadmium, a non-specific calcium channel blocker, or nimodipine, a specific L-type calcium channel blocker. Membrane resealing was assessed by the changes of membrane potential and compound action potential (CAP), and exclusion of horseradish peroxidase 60 min following trauma. Furthermore, 1 microM BayK 8644, a VDCC agonist, significantly enhanced membrane resealing. Interestingly, this effect was completely abolished when the concentration of BayK 8644 was increased to 30 microM. These data suggest that VDCC play a critical role in membrane resealing. Further, there is likely an appropriate range of calcium influx through VDCC which ensures effective axonal membrane resealing. Since elevated intracellular calcium has also been linked to axonal deterioration, blockage of VDCC is proposed to be a clinical treatment for various injuries. The knowledge gained in this study will likely help us better understand the role of calcium in various CNS trauma, which is critical for designing new approaches or perhaps optimizing the effectiveness of existing methods in the treatment of CNS trauma.
Nehrt
A
A
Center for Paralysis Research, Department of Basic Medical Sciences, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Rodgers
R
R
Shapiro
S
S
Borgens
R
R
Shi
R
R
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002104:Cadmium / Q000008:administration & dosage; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009553:Nimodipine / Q000008:administration & dosage; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002104:Cadmium; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium