The effective therapeutics for the sinoatrial node (SAN) pacemaker dysfunction induced by SCN5A gene mutation this is still being explored recently. In this study, a two-dimensional experimental model of rabbit SAN-atrial cell system which proposed by Zhang et al., was used as a prototype, the gene mutation was considered, and effects of both the acid concentration and temperature were also introduced. The effects of acid concentration and temperature on sick sinus syndrome (SSS) at the tissue level were investigated by simulation. The results showed that the SAN abnormal pacemaker could be caused by the reduction of I(Na), which is induced by the two mutations of T220I and delF1617. The results also showed that if we properly adjusted the acid concentration and temperature of the system, not only could we increase the relevant currents, but also could we increase I(Na) which reduced by gene mutations, so that the pacemaking behavior of SAN tissue could return to normal state from abnormalities. The above simulation results imply that the abnormal pacemaking of SAN system may closely relate to the gene mutation of ion channel mutations, and the acid concentration and temperature may play a modulatory role. Our study could be useful for clinical medical diagnosis and therapy of cardiac disease.