抄録
β-adrenergic receptor agonists, such as isoproterenol, activate protein kinase A (PKA) and induce positive inotropy in the ventricular myocyte. Major mechanisms underlying the positive inotropy are enhanced activities of the sarcolemmal L-type Ca2+ channel (ICaL) and the sarcoplasmic reticulum Ca2+-ATPase via phosphorylation of phospholamban. However, role of activation of cystic fibrosis transmembrane conductance regulator channel (ICFTR) in the inotropic effect has not been well understood.We have constructed a computer model of β-adrenergic signaling network including PKA activation of ICaL, phospholamban and ICFTR based on Saucerman et al., (2003, 2004) and implemented it into Kyoto model (Matsuoka et al., 2004). When 1 μM isoproterenol was applied, the amplitudes of ICaL, Ca2+ transient, and cell shortening were increased, and the action potential duration was prolonged. Elimination of the activation of ICFTR resulted in a slight rise of the plateau phase of action potential and a decrease in the amplitudes of ICaL due to the decrease in driving force. Ca2+ transient was attenuated by about 20%. The results demonstrate that the activation of ICFTR induces compensatory increase in ICaL and facilitates indirectly the positive inotropic action of isoproterenol. [J Physiol Sci. 2006;56 Suppl:S129]
