Abstract
Positive chronotropy induced by β1-adrenergic stimulation is achieved by multiple interactions of ion channels and transporters in pacemaker cells. In order to investigate roles of the ion channels and transporters and their interactions in the chronotropy quantitatively, we updated our SA node cell model developed in 2003 and incorporated β1-adrenergic signaling cascade. Firstly, the validity of the model was reviewed by comparing behavior and parameters of the model with experimental data. Secondly, the response to β1-adrenergic stimulation was analyzed by isoprenaline (ISO) application, which enhanced multiple currents and increased firing frequency. From the analysis of enhanced currents during the stimulation, it was concluded that the L-type Ca2+ current (ICaL), the sustained inward current (Ist) and the hyperpolarization-activated cation current (Iha) played major roles in increasing the inward current during slow diastolic potential and thus increasing the firing rate. On the other hand, IKs was important to counterbalance increased inward currents especially in repolarizing phase of action potentials. The alteration of Ca2+ dynamics during the stimulation was also calculated in the model. It was suggested that the Ca2+ release from sarcoplasmic reticulum (SR) played a minor role in inducing chronotropic effect in our model. [J Physiol Sci. 2008;58 Suppl:S179]
