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PMID: 22732308 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons.

The Journal of general physiology ·Vol. 140 ·No. 1 ·2012-07-00 ·Pages 3-15

Dibattista M, Amjad A, Maurya DK, Sagheddu C, Montani G, Tirindelli R, Menini A

Abstract

The rodent vomeronasal organ plays a crucial role in several social behaviors. Detection of pheromones or other emitted signaling molecules occurs in the dendritic microvilli of vomeronasal sensory neurons, where the binding of molecules to vomeronasal receptors leads to the influx of sodium and calcium ions mainly through the transient receptor potential canonical 2 (TRPC2) channel. To investigate the physiological role played by the increase in intracellular calcium concentration in the apical region of these neurons, we produced localized, rapid, and reproducible increases in calcium concentration with flash photolysis of caged calcium and measured calcium-activated currents with the whole cell voltage-clamp technique. On average, a large inward calcium-activated current of -261 pA was measured at -50 mV, rising with a time constant of 13 ms. Ion substitution experiments showed that this current is anion selective. Moreover, the chloride channel blockers niflumic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid partially inhibited the calcium-activated current. These results directly demonstrate that a large chloride current can be activated by calcium in the apical region of mouse vomeronasal sensory neurons. Furthermore, we showed by immunohistochemistry that the calcium-activated chloride channels TMEM16A/anoctamin1 and TMEM16B/anoctamin2 are present in the apical layer of the vomeronasal epithelium, where they largely colocalize with the TRPC2 transduction channel. Immunocytochemistry on isolated vomeronasal sensory neurons showed that TMEM16A and TMEM16B coexpress in the neuronal microvilli. Therefore, we conclude that microvilli of mouse vomeronasal sensory neurons have a high density of calcium-activated chloride channels that may play an important role in vomeronasal transduction.

MeSH Terms
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology Acetates/pharmacology Animals Anoctamin-1 Anoctamins Calcium/metabolism Cells, Cultured Chelating Agents/pharmacology Chloride Channel Agonists Chloride Channels/antagonists & inhibitors,metabolism Ethylenediamines/pharmacology HEK293 Cells Humans Ion Channel Gating/drug effects Mice Microvilli/metabolism Niflumic Acid/pharmacology Patch-Clamp Techniques Photolysis Sensory Receptor Cells/cytology,metabolism,physiology TRPC Cation Channels/metabolism Vomeronasal Organ/cytology,metabolism,physiology
Chemicals
ANO1 protein, mouse ANO2 protein, mouse Acetates Anoctamin-1 Anoctamins Chelating Agents Chloride Channel Agonists Chloride Channels Ethylenediamines TRPC Cation Channels Trpc2 protein, mouse DM-nitrophen Niflumic Acid 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dibattista Michele
Neurobiology Sector and Italian Institute of Technology Unit, Scuola Internazionale Superiore di Studi Avanzati (SISSA), 34136 Trieste, Italy.
Amjad Asma
Maurya Devendra Kumar
Sagheddu Claudia
Montani Giorgia
Tirindelli Roberto
Menini Anna
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Article Info
Journal
The Journal of general physiology
Abbr.
J Gen Physiol
ISSN
1540-7748
DOI
10.1085/jgp.201210780
Published
2012-07-00
Pages
3-15
Language
English
Region
United States
NLM ID
2985110R
PMCID
PMC3382724
Subset
IM
External Links
PubMed source DOI: 10.1085/jgp.201210780 PMC Full Text View journal details
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