Calcium-dependent electrostatic control of anion access to the pore of the calcium-activated chloride channel TMEM16A.

ABSTRACT: TMEM16A is a ligand-gated anion channel that is activated by intracellular Ca²⁺. This channel comprises two independent pores and closely apposed Ca²⁺ binding sites that are contained within each subunit of a homodimeric protein. Previously we characterized the influence of positively charged pore-lining residues on anion conduction (Paulino et al., 2017a). Here, we demonstrate the electrostatic control of permeation by the bound calcium ions in mouse TMEM16A using electrophysiology and Poisson-Boltzmann calculations. The currents of constitutively active mutants lose their outward rectification as a function of Ca²⁺ concentration due to the alleviation of energy barriers for anion conduction. This phenomenon originates from Coulombic interactions between t

SUBMITTER: Lam AK 

PROVIDER: S-EPMC6195346 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature