Calcium-Activated Chloride Channels (CaCCs) Regulate Action Potential and Synaptic Response in Hippocampal Neurons

• Published in: Neuron (Cambridge, Mass.) Vol. 74; no. 1; pp. 179 - 192
• Main Authors: Huang, Wendy C., Xiao, Shaohua, Huang, Fen, Harfe, Brian D., Jan, Yuh Nung, Jan, Lily Yeh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.04.2012; Elsevier Limited
• Subjects: Action potential; Action Potentials - physiology; Animals; Anoctamin-1; Anoctamins; Calcium; Calcium - metabolism; Calcium channels; Calcium Channels - metabolism; Calcium influx; chloride channels (calcium-gated); Chloride Channels - physiology; Experiments; Feedback; Glutamic acid receptors (ionotropic); Hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Ion channels; Learning; Memory; Mice; N-Methyl-D-aspartic acid receptors; Neurogenesis; Neuromodulation; Neurons; Neurotransmitter release; Pyramidal Cells - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Synapses; Synaptic Potentials - physiology; Transmitters
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2012.01.033

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. ► There are calcium-activated chloride channels in hippocampal pyramidal neurons ► CaCCs shorten action potential duration ► CaCCs dampen EPSP, impede summation, and raise threshold for EPSP-spike coupling ► TMEM16B, not TMEM16A, is important for CaCC function in hippocampal pyramidal neurons Neuronal signaling via action potentials and synaptic potentials may be subject to feedback regulation by ion channels activated by calcium. Huang et al. show that the TMEM16B calcium-activated chloride channels control action potential waveform and synaptic efficacy in hippocampal neurons.