PT  - JOURNAL ARTICLE
AU  - Tembo, Maiwase
AU  - Lara-Santos, Crystal
AU  - Rosenbaum, Joel C.
AU  - Carlson, Anne E.
TI  - PIP<sub>2</sub> and Ca<sup>2+</sup> regulation of TMEM16A currents in excised inside-out patches
AID  - 10.1101/2022.08.30.505925
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.30.505925
4099  - http://biorxiv.org/content/early/2022/09/02/2022.08.30.505925.short
4100  - http://biorxiv.org/content/early/2022/09/02/2022.08.30.505925.full
AB  - The Ca2+ activated Cl− channel formed by transmembrane member 16A (TMEM16A) is broadly expressed and regulates diverse processes. In addition to Ca2+, TMEM16A channels require the acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) to open. Like other channels regulated by PI(4,5)P2, TMEM16A-conducted currents recorded in excised patches slowly decay overtime. Here we assessed how intracellular Ca2+ alters the rate of this current rundown, using the channels endogenously expressed in oocytes from the African clawed frog, Xenopus laevis. We found that in excised, inside-out patches, the concentration of applied Ca2+ alters the rate of rundown, with high Ca2+ concentrations speeding rundown by activating membrane associated phospholipase C (PLC). Together, these results clarify our understanding of how Ca2+ regulates both TMEM16A directly, and targets PLC to regulate the membrane PI(4,5)P2 content.Competing Interest StatementThe authors have declared no competing interest.