Upregulation of L-type Ca2+ channels in reactive astrocytes after brain injury, hypomyelination, and ischemia.
Anti-peptide antibodies that specifically recognize the alpha1 subunit of class A-D voltage-gated Ca2+ channels and a monoclonal antibody (MANC-1) to the alpha2 subunit of L-type Ca2+ channels were used to investigate the distribution of these Ca2+ 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 alpha2 subunit of L-type Ca2+ channels by the MANC-1 antibody was increased in reactive astrocytes in each of these forms of brain injury. The alpha1C subunits of class C L-type Ca2+ channels were upregulated in reactive astrocytes located in the affected regions in each of these models of brain injury, although staining for the alpha1 subunits of class D L-type, class A P/Q-type, and class B N-type Ca2+ 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 Ca2+ channels in neurons. The upregulation of L-type Ca2+ 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.
Westenbroek
R E
RE
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
Bausch
S B
SB
Lin
R C
RC
Franck
J E
JE
Noebels
J L
JL
Catterall
W A
WA
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D015220:Calcium Channels / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D018690:Excitatory Amino Acid Agonists; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005911:Gliosis / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006358:Hot Temperature; D007276:Injections, Intraventricular; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009186:Myelin Sheath / Q000473:pathology*; D051381:Rats; D015854:Up-Regulation / Q000502:physiology; D014951:Wounds, Stab / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D007608:Kainic Acid