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Calcium-Activated Chloride Channels (CaCCs) regulate action potential and synaptic responses in hippocampal pyramidal neurons

Abstract

Neurons rely on action potentials for propagating signals and synaptic potentials for responding to other neurons. The calcium influx during these electrical events opens calcium-activated ion channels for feedback regulation. Here we identify calcium-activated chloride channels (CaCCs) to be a novel mechanism of calcium-dependent feedback regulation in hippocampal neurons. We provide the first evidence that CaCCs are present in these neurons and demonstrate that CaCCs are activated during neuronal signaling to shorten action potentials and dampen excitatory synaptic potentials. Having recently identified TMEM16A and TMEM16B as CaCCs, we further show that TMEM16B but not TMEM16A is important for hippocampal CaCC, thus laying the groundwork for deciphering the dynamic CaCC modulation of neuronal signaling in hippocampal neurons important for learning and memory.

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