Fig. 8.

Illustration of the binding site and opening of LGCC in response to IVM. (A) Five GluCl subunits, each consisting of four alpha helical structures (M1-M4) and an extracellular domain not shown here, adopt a pentameric tertiary structure. The transmembrane region is arranged with each subunit perpendicular to the plane of the membrane and the M2 helices (orange cylinders) of each subunit lining the interior channel. Chloride ions (green circles) flow down the concentration gradient (indicated by the green arrow) when IVM (yellow/orange wedge) binds at the interface of two GluCl subunits, inducing a shift in the helices and tilting of the M2 helices away from the center of the channel, effectively widening the extracellular portion of the channel. (B) An illustration of the electrophysiological response of GluCl to IVM. The closed state is represented by a static electrical potential (flat line) and circle with narrow pore, precluding chloride ion flow. Addition of IVM (yellow/orange arrow) induces an irreversible open channel conformation, illustrated by the right part of the trace and the circle with a large pore.