The α7 Nicotinic Acetylcholine Receptor: Computational Modeling of Channel Gating

Abstract

The alpha nicotinic acetylcholine receptor is a common receptor in the brain, and it permits the flow of calcium ions. Studies have shown that the alpha receptor plays an important role in the central nervous system and may be used to treat neurological diseases. Despite recent advances in our understanding of alpha physiology and biochemistry, we still lack a coherent model of these channels' regulation. In this project, we aim to develop a computational model for the alpha channels. The opening of these channels has been reported to be dependent on both extracellular calcium and acetylcholine, in which the openings are more frequent in the presence of extracellular calcium and acetylcholine. Because the opening of alpha channels is random, we hypothesize that a stochastic model will precisely reproduce their activity. We proposed a four-state model with two closed states C1 and C2, as well as two open states O1 and O2. During the resting phase, all âº7 channels are in states C1 and C2; however, with the entrance of ACh, the transition from C1 to O1 occurs. The activation from C2 to O2 is also accompanied by a rise in extracellular Ca2+. In the future, we will complete the stochastic model to match our model findings to the experimental data, and we believe that our discoveries will aid in the development of neurological therapies.