Coupling of TRPV6 and TMEM16A in epithelial principal cells of the rat epididymis
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AbstractThe epididymis establishes a congenial environment for sperm maturation and protection. Its fluid is acidic, and
the calcium concentration is low and declines along the length of the epididymal tubule. However, our knowledge
of ionic currents and mechanisms of calcium homeostasis in rat epididymal epithelial cells remains enigmatic.
In this study, to better understand calcium regulation in the epididymis, we use the patch-clamp method
to record from single rat cauda epididymal principal cells. We detect a constitutively active Ca2+ current with
characteristics that match the epithelial calcium channel TRPV6. Electrophysiological and pharmacological data
also reveal a constitutively active calcium-activated chloride conductance (CaCC). Removal of extracellular calcium
attenuates not only the TRPV6-like conductance, but also the CaCC. Lanthanide block is time dependent
such that the TRPV6-like component is inhibited first, followed by the CaCC. The putative CaCC blocker niflumic
acid partially inhibits whole-cell currents, whereas La3+ almost abolishes whole-cell currents in principal cells.
Membrane potential measurements reveal an interplay between La3+-sensitive ion channels and those that are
sensitive to the specific TMEM16A inhibitor tannic acid. In vivo perfusion of the cauda epididymal tubule shows
a substantial rate of Ca2+ reabsorption from the luminal side, which is dose-dependently suppressed by ruthenium
red, a putative blocker of epithelial Ca2+ channels and CaCC. Finally, we discover messenger RNA for both
TRPV6 and TMEM16A in the rat epididymis and show that their proteins colocalize in the apical membrane of
principal cells. Collectively, these data provide evidence for a coupling mechanism between TRPV6 and TMEM16A
in principal cells that may play an important role in the regulation of calcium homeostasis in the epididymis.
Acceptance Date28/06/2016
All Author(s) ListDa Yuan Gao, Bao Li Zhang, Matthew C.T. Leung, Simon C.L. Au, Patrick Y.D. Wong, Winnie W.C. Shum
Journal nameJournal of General Physiology
Year2016
Month8
Day1
Volume Number148
Issue Number2
PublisherRockefeller University Press
Place of PublicationUSA
Pages161 - 182
ISSN0022-1295
eISSN1540-7748
LanguagesEnglish-United States

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