The journal of physiological sciences : JPS
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Positive chronotropy induced by beta1-adrenergic stimulation is achieved by multiple interactions of ion channels and transporters in sinoatrial node pacemaker cells (SANs). To investigate the ionic mechanisms, we updated our SAN model developed in 2003 and incorporated the beta1-adrenergic signaling cascade developed by Kuzumoto et al. (2007). Since the slow component of the delayed rectifier K+ current (IKs) is one of the major targets of the beta1-adrenergic cascade, we developed a guinea pig model with a large IKs. ⋯ This was because the activation of IKs during the preceding action potential was negligibly small. However, IKs was important in counterbalancing the increase in ICaL and the Na+/Ca2+ exchange current (INaCa), which otherwise compromised the positive chronotropic effect by elongating the action potential duration. Enhanced Ca2+ release from the sarcoplasmic reticulum failed to induce an obvious chronotropic effect in our model.