title: Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.
abstract: Calcium-activated chloride channels of the anoctamin (alias TMEM16) protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.
authors.affiliation: Department of Animal Molecular Physiology, Centre of Organismal Studies, Im Neuenheimer Feld 504, Heidelberg University, Heidelberg, Germany.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Animal Molecular Physiology, Centre of Organismal Studies, Im Neuenheimer Feld 504, Heidelberg University, Heidelberg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmelzeisen
authors.affiliation: Department of Animal Molecular Physiology, Centre of Organismal Studies, Im Neuenheimer Feld 504, Heidelberg University, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Parthier
authors.affiliation: Department of Animal Molecular Physiology, Centre of Organismal Studies, Im Neuenheimer Feld 504, Heidelberg University, Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Frings
authors.affiliation: Department of Animal Molecular Physiology, Centre of Organismal Studies, Im Neuenheimer Feld 504, Heidelberg University, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Möhrlen
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D000075368:Anoctamins; D001692:Biological Transport; D002525:Cerebellar Cortex / Q000378:metabolism / Q000502:physiology*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008564:Membrane Potentials; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: C531181:ANO1 protein, mouse; C532161:ANO2 protein, mouse; D000075369:Anoctamin-1; D000075368:Anoctamins; D018118:Chloride Channels; D002712:Chlorides