Structural and mechanistic tuning of synaptic responses by homomeric Cys-loop receptors

BOUZAT C; BARTOS M; CORRADI J; SINE SM

San Diego, California

Congreso; Neuroscience 2007; 2007

Society for Neuroscience

Following the synaptic release and binding of neurotransmitter to Cys-loop receptors, the post-synaptic response is governed by the kinetics of channel activation, deactivation and desensitization. Here we measure unitary and macroscopic currents through homomeric alpha7 and 5-HT3A Cys-loop receptor channels. Single channel openings of alpha7 receptors are brief and terminate in a long-lived desensitized state whereas openings of 5-HT3A receptors are long and terminate by return to the resting state. By generating chimeric receptors and substituting structural loops at the junction of the ligand binding and pore domains, we find parallel changes in desensitization onset and channel open times caused by a dynamic interplay among structural loops. Thus the structure of the binding-pore interface varies among types of homomeric receptors to allow termination of synaptic responses through either desensitization or return to the resting state, thus controlling the stimulation refractory period.