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Neuron. 2012 Apr 12;74(1):179-92. doi: 10.1016/j.neuron.2012.01.033.

Calcium-activated chloride channels (CaCCs) regulate action potential and synaptic response in hippocampal neurons.

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  • 1Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.


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.

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