Dependence of Miniature Endplate Current on Kinetic Parameters of Acetylcholine Receptors Activation: A Model Study

Mathematical modeling was applied to study the dependence of miniature endplate current (MEPC) amplitude and temporal parameters on the values of the rate constants of acetylcholine binding to receptors (k₊) when cholinesterase was either active or inactive. The simulation was performed under two different sets of parameters describing acetylcholine receptor activation–one with high and another with low probability (Po_high and Po_low) of receptor transition into the open state after double ligand binding. The dependence of model MEPC amplitudes, rise times, and decay times on k₊ differs for set Po_low and set Po_high. The main outcome is that for set Po_high, the rise time is significantly longer at low values of k₊ because of the prolongation of ACh diffusion time to the receptor. For the set Polow, the rise time is shorter at low values of k1, which can be explained by the small probability of AChR forward isomerization after ACh binding and faster MEPC's peak formation.