title: Calcium-activated chloride channels (CaCCs) regulate action potential and synaptic response in hippocampal neurons.
abstract: Central neurons respond to synaptic inputs from other neurons by generating synaptic potentials. Once the summated synaptic potentials reach threshold for action potential firing, the signal propagates leading to transmitter release at the synapse. The calcium influx accompanying such signaling opens calcium-activated ion channels for feedback regulation. Here, we report a mechanism for modulating hippocampal neuronal signaling that involves calcium-activated chloride channels (CaCCs). We present evidence that CaCCs reside in hippocampal neurons and are in close proximity of calcium channels and NMDA receptors to shorten action potential duration, dampen excitatory synaptic potentials, impede temporal summation, and raise the threshold for action potential generation by synaptic potential. Having recently identified TMEM16A and TMEM16B as CaCCs, we further show that TMEM16B but not TMEM16A is important for hippocampal CaCC, laying the groundwork for deciphering the dynamic CaCC modulation of neuronal signaling in neurons important for learning and memory.
authors.affiliation: Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Huang
authors.forename: Shaohua
authors.initials: S
authors.lastname: Xiao
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000075369:Anoctamin-1; D000075368:Anoctamins; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D018118:Chloride Channels / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D017966:Pyramidal Cells / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D055366:Synaptic Potentials / Q000502:physiology*
chemical_list: C531181:ANO1 protein, mouse; C532161:ANO2 protein, mouse; D000075369:Anoctamin-1; D000075368:Anoctamins; D015220:Calcium Channels; D018118:Chloride Channels; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium