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.
Kawada
Toru
T
Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. torukawa@res.ncvc.go.jp
Akiyama
Tsuyoshi
T
Shimizu
Shuji
S
Kamiya
Atsunori
A
Uemura
Kazunori
K
Sata
Yusuke
Y
Shirai
Mikiyasu
M
Sugimachi
Masaru
M
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D018738:Hexamethonium / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D018738:Hexamethonium; C064719:iberiotoxin; D000109:Acetylcholine