Large conductance Ca2+-activated K+ channels inhibit vagal acetylcholine release at the rabbit sinoatrial node

Although large conductance Ca(2+)-activated K(+) (BK) channels play an important role in determining vascular tone, their role in the efferent cardiac vagal system remains to be elucidated. In anesthetized rabbits (n=9), acetylcholine (ACh) was measured at the right atrium near the sinoatrial node by a cardiac microdialysis technique, and the ACh release in response to electrical stimulation of the cervical preganglionic vagal nerves was examined. Local administration of a BK channel blocker iberiotoxin (2 microM) through a dialysis fiber increased the stimulation-induced ACh release from 7.6+/-2.7 to 9.0+/-3.2 nM (P<0.05). Addition of intravenous administration of iberiotoxin (0.11 mg/body) did not increase the stimulation-induced ACh release further (10.8+/-4.4 nM). These results indicate that the BK channels play an inhibitory role in the vagal ACh release to the sinoatrial node.