A model for the dynamics of nicotinic acetylcholine receptor ion channels

I. BERDAKIN; C. A. CONDAT; H. R. ARIAS

Pharmacology of Nicotinic Acetylcholine Receptor from the Basic and Therapeutic Perspectives

Signpost

Lugar: Kerala; Año: 2011;

A host of models have been developed to describe the dynamics of nicotinic receptor ionic channels after agonist activation. The biophysical content of these models has increased as new experimental techniques have shed light on the structure and on some of the relevant time-dependent processes that occur inside the ion channel. In this chapter we show how the defect-diffusion model has evolved from a mostly mathematical construct designed to fit electrophysiological data to a robust if perfectible description of the conformational events that determine the gating behavior in nicotinic acetylcholine receptors. The defect is now interpreted as a conformational solitary wave activated by the binding of the agonist, which performs a Brownian motion along the longitudinal axis of the protein and catalyzes channel opening and subsequently channel closing. Agonist-induced receptor desensitization can be interpreted as a change in the energetic landscape that deforms or even destroys the solitary wave.