Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors.

ABSTRACT: AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic neurological disorders. However, despite the clinical importance, the therapeutic landscape for specifically targeting them, and not the calcium-impermeable AMPA receptors, remains largely undeveloped. To address this problem, we used cryo-electron microscopy and electrophysiology to investigate the mechanisms by which small-molecule blockers selectively inhibit ion channel conductance in calcium-permeable AMPA receptors. We determined the structures of calcium-permeable GluA2 AMPA receptor complexes with the auxiliary subunit stargazin bound to channel blockers, including the orb weaver spider t

SUBMITTER: Twomey EC 

PROVIDER: S-EPMC6181147 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature