LOCAL CHOLINERGIC SUPPRESSION OF PACEMAKER ACTIVITY IN THE RABBIT SINOATRIAL NODE

The effects of transmural vagal stimulation and acetylcholine (ACh) su perfusion on primary and latent pacemaker cells of the rabbit sinoatri al node were studied by using microelectrodes. Both ACh and vagal stim ulation lengthened atrial cycle length by 40-60% as compared with cont rol. In the cells from the primary pacemaker area, both ACh superfusio n and vagal stimulation suppressed action potential (AP) amplitude and then induced inexcitability. In contrast, cells from subsidiary pacem aker area as well as atrium remained excitable. These effects were com pletely reversible and also were abolished by atropine, 10(-7) M. Chol inergically induced suppression of AP amplitude is predictable based o n the maximal rate of AP upstroke (dV/dt). The probability of amplitud e suppression was the highest among pacemaker cells (dV/dt, <3 V/s), i n which ACh suppressed amplitude in 27 (93%) of 29 cells, and vagal st imulation did so in 38 (81%) of 47 cells. With increasing upstroke vel ocity, the probability of amplitude suppression decreased. Inexcitabil ity did not occur in cells whose dV/dt was >15 V/s. The suppression of AP amplitude by ACh occurred in a concentration-dependent manner: the concentration inducing suppression of amplitude in 50% of pacemaker c ells was approximate to 10 mu M. These results indicate that cholinerg ic effects on typical pacemaker and subsidiary pacemaker cells are dif ferent: whereas subsidiary pacemaker cells remain excitable, typical p acemaker cells become quiescent. We hypothesize that quiescent cells c reate quiescent regions in the center of the sinoatrial node that migh t functionally be an obstacle for reentrant tachycardias.