PACEMAKING IN THE HEART - THE INTERPLAY OF IONIC CURRENTS

1, There is still a degree of controversy about which currents drive p acemaking in the sinoatrial node or sinus venosus, Early attempts to i dentify a single 'pacemaker current' in these tissues, based on voltag e-clamp data, were largely unsuccessful, prompting the search for othe r mechanisms that may contribute to rhythmic activity. 2. Whole-cell p atch-clamp recording from single cells isolated from the sinus venosus of the toad has shown that a voltage-dependent sodiun current may pla y a role in pacemaking. This current has a transient component that co ntributes to the action potential upstroke and an inactivation-resista nt component that contributes to the diastolic depolarization. The rel ative importance of this current in pacemaking is still controversial. 3, The development of computer models of pacemaking has contributed g reatly to our understanding of how ionic currents can interact to prod uce rhythmic activity. Results are presented from one such model, 'Oxs oft Heart', to illustrate the different contributions of I-f and I-Na and to highlight the concept that pacemaking is driven by the integrat ed activity of many processes, rather than by any one current in parti cular. 4, Present models of pacemaking fail to accurately reproduce bi ological observations for certain situations. It is becoming clear tha t many processes contribute to pacemaking and have yet to be fully inc orporated into models, Recent results regarding the role of intracellu lar calcium buffering and release and their implications, are discusse d in this context. 5, The control of pacemaking by neurotransmitters i s discussed. The limitations of single cell models in reproducing many of the complex responses to nerve stimulation of multicellular tissue , such as postinhibitory rebound, are discussed and possible improveme nts to models are suggested.