TMEM16A alternative splicing isoforms in Xenopus tropicalis: Distribution and functional properties

•Oocytes of X. tropicalis oocytes present an outwardly-rectifying Cl− current.•This current may be partially attributed to the expression of the TMEM16A channel.•Five alternatively spliced isoforms of TMEME16A were identified and expressed in HEK-293 cells.•The TMEM16A isoforms are widely expressed in different tissues. Oocytes of Xenopus tropicalis elicit a Ca2+-dependent outwardly rectifying, low-activating current (ICl,Ca) that is inhibited by Cl− channel blockers. When inactivated, ICl,Ca shows an exponentially decaying tail current that is related to currents generated by TMEM16A ion channels. Accordingly, RT-PCR revealed the expression of five alternatively spliced isoforms of TMEM16A in oocytes, which, after expression in HEK-293 cells, gave rise to fully functional Cl− channels. Upon hyperpolarization to −80mV a transient current was observed only in isoforms that carry the exon 1d, coding for two potentially phosphorylatable Threonine residues. The identified isoforms are differentially expressed in several tissues of the frog. Thus, it appears that X. tropicalis oocytes express TMEM16A that gives rise to a Ca2+-dependent Cl− current, which is different from the previously reported voltage-dependent outwardly rectifying Cl− current.