Abstract
G-protein-gated potassium (KG) channel,which is directly activated by G-protein βγ subunits,and is responsible for cholinergic regulation of heart beats.Cardiac KG channel is known to exhibit a characteristic apparentvoltage-dependent behavior, named "relaxation", which has been shown toreflect the voltage-dependent control of receptor mediated cyclic reactionof G-protein (G-protein-cycle) by regulators of G-protein signaling (RGS)proteins. Based on these results, we have succeeded in establishing aphysiological G-protein-cycle model.We use the Monod-Wyman-Changeux allosteric model for the interaction between theKG channel and the heterotrimeric G-protein βγ subunit.The parameters of the allosteric model are estimated by the experimental results(Corey and Clapham, 2001) of the population distribution of the number of bindingGβγ with the GIRK4 homotetramer. The derived parameter set ofthe allosteric model is consistent with the dose-dependence of the channelactivity. The model of receptor-G-protein interaction is based on the modelpresented by Thomsen et al (1988). The rate constants of each reactions in theG-protein-cycle are decided to reproduce simultaneously both thedose-dependence of the steady-state channel activation and the time courseof the open probability. The physiological relevance of the relaxation behaviorin heart beat regulation can be evaluated by incorporating this model intoaction potential simulation, Luo-Rudy model. [Jpn J Physiol 54 Suppl:S133 (2004)]
