Phase sensitivity and entrainment studies in a cardiac pacemaker cell

We have extended our model of the single rabbit sinoatrial node (SAN) cell, to simulate cellular responses to bath applications of acetylcholine (ACh) and isoprenaline (ISO), as well as the effects of neuronally released ACh. Our modified model represents the single SAN cell in its normal milieu (an extracellular cleft space is provided containing a random distribution of parasympathetic neural varicosities). The model is utilized to predict the well known phase-sensitive response of the SAN cell to aperiodic and periodic pulses of ACh, in the presence and absence of the /spl beta/-agonist ISO. It has also been used to predict the response of the SAN cell to longer periods (5 sec) of periodic vagal stimulation, which results in the cessation of pacemaking. The model-generated responses under both of these conditions, agree quite closely with experimental results.