TMEM16F/ANO6, a Ca-activated anion channel, is negatively regulated by the actin cytoskeleton and intracellular MgATP.

Anoctamin 6 (ANO6/TMEM16F) is a recently identified membrane protein that has both phospholipid scramblase activity and anion channel function activated by relatively high [Ca]. In addition to the low sensitivity to Ca, the activation of ANO6 Cl conductance is very slow (>3-5 min to reach peak level at 10 μM [Ca]), with subsequent inactivation. In a whole-cell patch clamp recording of ANO6 current (I), disruption of the actin cytoskeleton with cytochalasin-D (cytoD) significantly accelerated the activation kinetics, while actin filament-stabilizing agents (phalloidin and jasplakinolide) commonly inhibited I.