Parasympathetic modulation of sinoatrial node pacemaker activity in rabbitheart: a unifying model

We have extended our compartmental model [Am. J. Physiol. 266 (Cell Physiol . 35): C832-C852, 1994] of the single rabbit sinoatrial node (SAN) cell so that it can simulate cellular responses to bath applications of ACh and iso prenaline as well as the effects of neuronally released ACh. The model empl oys three different types of muscarinic receptors to explain the variety of responses observed in mammalian cardiac pacemaking cells subjected to vaga l stimulation. The response of greatest interest is the ACh-sensitive chang e in cycle length that is not accompanied by a change in action potential d uration or repolarization or hyperpolarization of the maximum diastolic pot ential. In this case, an ACh-sensitive K+ current is not involved. Membrane hyperpolarization occurs in response to much higher levels of vagal stimul ation, and this response is also mimicked by the model. Here, an ACh-sensit ive K+ current is involved. The well-known phase-resetting response of the SAN cell to single and periodically applied vagal bursts of impulses is als o simulated in the presence and absence of the beta-agonist isoprenaline. F inally, the responses of the SAN cell to longer continuous trains of period ic vagal stimulation are simulated, and this can result in the complete ces sation of pacemaking. Therefore, this model is 1) applicable over the full range of intensity and pattern of vagal input and 2) can offer biophysicall y based explanations for many of the phenomena associated with the autonomi c control of cardiac pacemaking.