Presynaptic Localization and Possible Function of Calcium-Activated Chloride Channel Anoctamin 1 in the Mammalian Retina

Calcium (Ca(2+))-activated chloride (Cl(-)) channels (CaCCs) play a role in the modulation of action potentials and synaptic responses in the somatodendritic regions of central neurons. In the vertebrate retina, large Ca(2+)-activated Cl(-) currents (ICl(Ca)) regulate synaptic transmission at photor...

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Published in:	PloS one 2013-06, Vol.8 (6), p.e67989-e67989
Main Authors:	Jeon, Ji Hyun, Paik, Sun Sook, Chun, Myung-Hoon, Oh, Uhtaek, Kim, In-Beom
Format:	Article
Language:	eng
Subjects:	Acids Action Potentials Animals Anoctamin-1 Benzoic acid Biology Bipolar cells Calcium Calcium - metabolism Calcium channels (L-type) Calcium chloride Calcium signalling Carbon dioxide Chloride Chloride channels (calcium-gated) Chloride Channels - metabolism Cobalt Current injection Depolarization Immunoreactivity Localization Male Mammals Medical research Medicine Membrane potential Mice Mice, Inbred C57BL Nervous system Nervous tissues Neurons Neurosciences Nifedipine Patch-Clamp Techniques Photoreceptors Physiology Presynaptic Terminals - metabolism Retina Retina - metabolism Synaptic transmission Synaptic Transmission - physiology Terminals Tissues
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Summary:	Calcium (Ca(2+))-activated chloride (Cl(-)) channels (CaCCs) play a role in the modulation of action potentials and synaptic responses in the somatodendritic regions of central neurons. In the vertebrate retina, large Ca(2+)-activated Cl(-) currents (ICl(Ca)) regulate synaptic transmission at photoreceptor terminals; however, the molecular identity of CaCCs that mediate ICl(Ca) remains unclear. The transmembrane protein, TMEM16A, also called anoctamin 1 (ANO1), has been recently validated as a CaCC and is widely expressed in various secretory epithelia and nervous tissues. Despite the fact that tmem16a was first cloned in the retina, there is little information on its cellular localization and function in the mammalian retina. In this study, we found that ANO1 was abundantly expressed as puncta in 2 synaptic layers. More specifically, ANO1 immunoreactivity was observed in the presynaptic terminals of various retinal neurons, including photoreceptors. ICl(Ca) was first detected in dissociated rod bipolar cells expressing ANO1. ICl(Ca) was abolished by treatment with the Ca(2+) channel blocker Co(2+), the L-type Ca(2+) channel blocker nifedipine, and the Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and niflumic acid (NFA). More specifically, a recently discovered ANO1-selective inhibitor, T16Ainh-A01, and a neutralizing antibody against ANO1 inhibited ICl(Ca) in rod bipolar cells. Under a current-clamping mode, the suppression of ICl(Ca) by using NPPB and T16Ainh-A01 caused a prolonged Ca(2+) spike-like depolarization evoked by current injection in dissociated rod bipolar cells. These results suggest that ANO1 confers ICl(Ca) in retinal neurons and acts as an intrinsic regulator of the presynaptic membrane potential during synaptic transmission.
ISSN:	1932-6203 1932-6203