Mathematical studies of the effects of acetylcholine on pacemaker activity in the mammalian sinoatrial node

The effect of acetylcholine (ACh) on ionic currents responsible for pacemaking activity at the sinoatrial node was investigated using a mathematical model based on the DiFrancesco Noble equations. Two membrane currents in particular were examined in detail. Inhibition of the slow-inward calcium current iCaf yielded an increase in maximum diastolic potential (contrary to experimental evidence) and resulted in a limited range of control over the cardiac period as intracellular processes began to dominate. Activation of an additional potassium current iK, ACh however, yielded a substantial degree of variation in cardiac period, and shifted the maximum diastolic potential more negative. We conclude that iK, Ach is the most plausible mechanism for ACh induced bradycardia in the mammalian sinoatrial node. It was also observed that intracellular processes which regulated free calcium levels contributed significantly to normal pacing activity.