Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Tuesday Speaker Abstracts

Physiological Implications of Anoctamin 1, a Calcium-activated Chloride Channel

Uhtaek Oh

1,2

Korea Institute of Science and Technology, Seoul, South Korea,

Seoul National University,

Seoul, South Korea.

Anoctamin 1 (ANO1/TMEM16A) is activated by intracellular Ca

and voltage. ANO1 is

expressed in epithelia of salivary glands, pancreas, kidney, pulmonary airways, the retina, and

sensory neurons. ANO1 is highly expressed in dorsal-root ganglion (DRG) neurons, suggesting a

role in nociception. ANO1 is activated by heat over 44oC. ANO1 is highly co-expressed with

TRPV1, a marker for nociceptors, suggesting the involvement in nociception. Ano1-deficient

mice specifically in DRG neurons were generated. Adv/Ano1fl/fl mice that have a functional

ablation of Ano1 mainly in DRG neurons showed reduced responses to painful heat. Thus,

ANO1 plays an important role in mediating nociception in sensory neurons. Itch is an unpleasant

sensation that evokes a desire to scratch. Because of high expression in nociceptors, ANO1 may

be involved in itch signals. We found that ANO1 also mediates itch. Adv/Ano1fl/fl mice showed

reduced scratching behaviors in response to non-histaminergic pruritic substances, but not to

histaminergic pruritogens. Cl- secretion is important for protection of intestinal epithelia.

Whether CaCC plays a role for the Cl- secretion in GI tracts is not known. When Ano1 is

abolished in small and large intestines, carbachol-induced Cl- conductance was significantly

reduced in duodenum, jejunum and proximal colon. The colon of Ano1 deficient mice was

edematous. Furthermore, when colitis was induced by dextran sodium sulfate (DSS), Ano1-

deficient mice developed severe colitis in colon. These results clearly suggest that ANO1 plays

an active role in secreting Cl- in intestines. In addition, ANO1 plays a critical role in

testosterone-induced benign prostate hyperplasia. Testosterone upregulates Ano1 transcripts

because there are few androgen-response elements in the promoter region of Ano1. In addition,

inhibition of ANO1 activity or downregulation of Ano1 reduced the size of testosterone-induced

prostates. Thus, it is clear that ANO1 mediates testosterone-induced prostate hyperalgesia.