Local cholinergic suppression of pacemaker activity in the rabbit sinoatrial node.
The effects of transmural vagal stimulation and acetylcholine (ACh) superfusion on primary and latent pacemaker cells of the rabbit sinoatrial node were studied by using microelectrodes. Both ACh and vagal stimulation lengthened atrial cycle length by 40-60% as compared with control. In the cells from the primary pacemaker area, both ACh superfusion and vagal stimulation suppressed action potential (AP) amplitude and then induced inexcitability. In contrast, cells from subsidiary pacemaker area as well as atrium remained excitable. These effects were completely reversible and also were abolished by atropine, 10(-7) M. Cholinergically induced suppression of AP amplitude is predictable based on the maximal rate of AP upstroke (dV/dt). The probability of amplitude suppression was the highest among pacemaker cells (dV/dt, <3 V/s), in which ACh suppressed amplitude in 27 (93%) of 29 cells, and vagal stimulation did so in 38 (81%) of 47 cells. With increasing upstroke velocity, the probability of amplitude suppression decreased. Inexcitability 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 cells was approximately 10 microM. These results indicate that cholinergic effects on typical pacemaker and subsidiary pacemaker cells are different: whereas subsidiary pacemaker cells remain excitable, typical pacemaker cells become quiescent. We hypothesize that quiescent cells create quiescent regions in the center of the sinoatrial node that might functionally be an obstacle for reentrant tachycardias.
Vinogradova
T M
TM
Heart Electrophysiology Laboratory, Institute of Experimental Cardiology, Moscow, Russia.
Fedorov
V V
VV
Yuzyuk
T N
TN
Zaitsev
A V
AV
Rosenshtraukh
L V
LV
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D008297:Male; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
D000109:Acetylcholine