MATHEMATICAL-MODEL OF ACETYLCHOLINE KINETICS IN NEUROEFFECTOR JUNCTIONS

Acetylcholine (ACh) kinetics in neuroeffector junctions (NEJ) of the s inus node plays a key role in vagal control of heart rate. Prior studi es have shown that the concentration of ACh ([ACh]) in. NEJ appears to follow first-order linear kinetics. To find out the reason why, we ex amine mathematically diffusion, degradation, and receptor binding of A Ch in NEJ. We identify seven conditions that potentially influence ACh kinetics. Because these conditions are satisfied for NEJ in the sinus node, 1) Me nonlinearity of ACh binding to muscarinic receptors has l ittle effect on [ACh]; 2) [ACh] does not depend on the distribution of acetylcholinesterase between the interstitial space and the pacemaker cells; 3) the interval from trough to subsequent peak [ACh] at the pa cemaker cells is negligible; 4) the mean [ACh] at the pacemaker cells is proportional to the frequency of vagal activity multiplied by Me am ount of ACh released per vagal stimulus and divided-by the rate coeffi cient of ACh degradation; and 5) [ACh] at pacemaker cells nearly follo ws first-order linear kinetics but does not at other sites in the NEJ. We conclude that earlier studies showed that [ACh] follows first-orde r linear kinetics, because they predicted [ACh] only at pacemaker cell s. ACh kinetics at other sites in the NEJ, such as at nerve endings, i s different.