Upregulation of L-Type Ca²⁺Channels in Reactive Astrocytes after Brain Injury, Hypomyelination, and Ischemia

Abstract

Anti-peptide antibodies that specifically recognize the α 1 subunit of class A–D voltage-gated Ca 2+ channels and a monoclonal antibody (MANC-1) to the α 2 subunit of L-type Ca 2+ channels were used to investigate the distribution of these Ca 2+ channel subtypes in neurons and glia in models of brain injury, including kainic acid-induced epilepsy in the hippocampus, mechanical and thermal lesions in the forebrain, hypomyelination in white matter, and ischemia. Immunostaining of the α 2 subunit of L-type Ca 2+ channels by the MANC-1 antibody was increased in reactive astrocytes in each of these forms of brain injury. The α 1C subunits of class C L-type Ca 2+ channels were upregulated in reactive astrocytes located in the affected regions in each of these models of brain injury, although staining for the α 1 subunits of class D L-type, class A P/Q-type, and class B N-type Ca 2+ channels did not change from patterns normally observed in control animals. In all of these models of brain injury, there was no apparent redistribution or upregulation of the voltage-gated Ca 2+ channels in neurons. The upregulation of L-type Ca 2+ channels in reactive astrocytes may contribute to the maintenance of ionic homeostasis in injured brain regions, enhance the release of neurotrophic agents to promote neuronal survival and differentiation, and/or enhance signaling in astrocytic networks in response to injury.