Connexin43 Hemichannels Mediate Secondary Cellular Damage Spread from the Trauma Zone to Distal Zones in Astrocyte Monolayers

被引：31

作者：

Rovegno, Maximiliano ^{[1
,2
]}

Soto, Paola A. ^{[3
]}

Saez, Pablo J. ^{[3
]}

Naus, Christian C. ^{[4
]}

Saez, Juan C. ^{[3
,5
]}

von Bernhardi, Rommy ^{[1
]}

机构：

[1] Pontificia Univ Catolica Chile, Fac Med, Dept Neurol, Lab Neurociencias, Santiago, Chile

[2] Pontificia Univ Catolica Chile, Fac Med, Dept Med Intens, Santiago, Chile

[3] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Fisiol, Santiago, Chile

[4] Univ British Columbia, Inst Life Sci, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada

[5] Ctr Interdisciplinario Neurociencias Valparaiso, Inst Milenio, Valparaiso, Chile

来源：

GLIA | 2015年 / 63卷 / 07期

关键词：

traumatic brain injury; connexins; P2; receptors; astroglia; apoptosis; GAP-JUNCTION HEMICHANNELS; STRETCH-INDUCED INJURY; CENTRAL-NERVOUS-SYSTEM; BRAIN-INJURY; CULTURED ASTROCYTES; PANNEXIN; CORTICAL ASTROCYTES; ATP RELEASE; NEURONS; CHANNELS;

D O I：

10.1002/glia.22808

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The mechanism of secondary damage spread after brain trauma remains unsolved. In this work, we redirected the attention to astrocytic communication pathways. Using an in vitro trauma model that consists of a scratch injury applied to an astrocyte monolayer, we found a significant and transient induction of connexin43 (Cx43) hemichannel activity in regions distal from the injury, which was maximal approximate to 1 h after scratch. Two connexin hemichannel blockers, La3+ and the peptide Gap26, abolished the increased activity, which was also absent in Cx43 KO astrocytes. In addition, the scratch-induced increase of hemichannel activity was prevented by inhibition of P2 purinergic receptors. Changes in hemichannel activity took place with a particular spatial distribution, with cells located at approximate to 17 mm away from the scratch presenting the highest activity (dye uptake). In contrast, the functional state of gap junction channels (dye coupling) was not significantly affected. Cx43 hemichannel activity was also enhanced by the acute extracellular application of 60 mM K+. The increase in hemichannel activity was associated with an increment in apoptotic cells at 24 h after scratch that was totally prevented by Gap26 peptide. These findings suggest that Cx43 hemichannels could be a new approach to prevent or reduce the secondary cell damage of brain trauma. GLIA 2015;63:1185-1199

引用

页码：1185 / 1199

页数：15