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Alternative Splicing of the murine Tmem16a Transcript in Heart
Author(s) -
O'Driscoll Kate Eileen,
Hatton William J,
Britton Fiona C
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1002.28
Subject(s) - exon , alternative splicing , chloride channel , gene isoform , ventricle , biology , gene , microbiology and biotechnology , genetics , medicine
TMEM16A and TMEM16B, members of a new family of proteins, have been shown to function as calcium‐activated chloride channels (Cl Ca ). Alternative exons were identified in the human TMEM16A transcript, which confer differences in the voltage‐ and calcium‐dependence of the channel. Calcium‐activated chloride currents (I ClCa ) are widely distributed in cardiac tissues and play important roles in cardiac excitability, yet the gene(s) encoding cardiac Cl Ca is unknown. We investigated the expression of Tmem16 paralogs in mouse heart and demonstrate that several family members, including Tmem16a , but not Tmem16b are expressed. We hypothesize that Tmem16a in its role as a Cl Ca , may contribute to this conductance in cardiac tissues. Quantitative RT‐PCR revealed that Tmem16a is more abundant in atria than ventricle. Three alternative exons of 66 bp, 12 bp and 78 bp were identified in the mouse Tmem16a transcript, which encode for additional channel regions. We performed exon‐specific RT‐PCR to identify the inclusion or exclusion of alternative exons in Tmem16a . Multiple Tmem16a channel isoforms consisting of various combinations of alternatively spliced exons were identified in atria and ventricle. The presence of Tmem16a variants and their different regional expression in heart raises the possibility that molecular diversity of cardiac Cl Ca may be generated by alternative Tmem16a channel structures.