Connexin-43 hemichannels contribute to the propagation of μ-calpain-mediated neuronal death in a cortical ablation injury model.

Abstract

We investigated the role of the astrocytic and neuronal hemichannels (HCs) in the spread of cortical neuronal death in a rat cortical injury model. Over time (by 6 h), propidium iodide (PI)-positive cells with labeling either with anti-neuron specific enolase or anti-parvalbumin (indicating GABAnergic interneurons) antibody spread in the deep cortical layers adjacent to the injury and co-localized with activated μ-calpain. Connexin (Cx)-43, glial fibrillary acidic protein (GFAP), activated μ-calpain and α-fodrin breakdown product (FBP) increased post-injury, peaking at 1 h, in the injury and adjacent areas. GFAP-Cx43-positive reactivated astrocytes exhibited similar distribution to the dead neurons. Cx43 and Cx36 primarily comprise HCs in the astrocyte and neuron, respectively. Ethidium bromide (EtBr) uptake was enhanced post-injury, and confirmed in the Cx43- and Cx36-positive cells. A Cx43-HC inhibitor Gap26 prevented the opening of the Cx43-HC and Cx36-HC, μ-calpain activation, α-fodrin proteolysis and death in the deep cortical neurons. Collectively, opening of the astrocytic Cx43-HC and neuronal Cx36-HC would induce the regional spread of cortical neuronal death through μ-calpain activation in the rat brain injury model.

• Authors: Yasuhiro Ishii, Kaori Shintani-Ishida, Ken-ichi Yoshida
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 441 Issue 2 Pg. 457-62 (Nov 15 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 24383076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Connexin 43
• Gap 26 peptide
• Gja1 protein, rat
• Glial Fibrillary Acidic Protein
• Microfilament Proteins
• Peptides
• fodrin
• Calpain
• mu-calpain

Topics

• Animals
• Apoptosis
• Astrocytes (metabolism, pathology)
• Brain Injuries (metabolism, pathology)
• Calpain (metabolism)
• Carrier Proteins (metabolism)
• Cerebral Cortex (injuries, metabolism, pathology)
• Connexin 43 (antagonists & inhibitors, genetics, metabolism)
• Disease Models, Animal
• Female
• Glial Fibrillary Acidic Protein (metabolism)
• Microfilament Proteins (metabolism)
• Neurons (metabolism, pathology)
• Peptides (pharmacology)
• Rats