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α3 and not α6 subunit containing nAChR mediate cardiac cholinergic ganglionic transmission
Author(s) -
Bibevski Steve,
Allocco Frances,
Deck Jennifer L.,
McIntosh J. Michael,
Dunlap Mark
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1201-b
Subject(s) - hexamethonium , cholinergic , superior cervical ganglion , neurotransmission , nicotinic agonist , medicine , endocrinology , acetylcholine , nicotinic acetylcholine receptor , chemistry , acetylcholine receptor , perfusion , neuromodulation , receptor , biology
The subunit composition of nicotinic acetylcholine receptors (nAChR) that mediate synaptic transmission in autonomic pathways remain incompletely elucidated. Conotoxin (ctx) MII blocks the majority (~70%) of cholinergic ganglionic transmission in vivo but acts on both α3/β2 and α6/β2 nAChR (only 5.6‐fold higher affinity for α3/β2 vs. α6/β2). We used a more specific nAChR blocker to investigate the hypothesis that α6/β2 nAChR play a functional role in ganglionic transmission. Methods 4 dogs were anesthetized and underwent cervical vagal nerve stimulations (VSTIM). The artery supplying the sinus node was perfused with Tyrodes solution in vivo . Sinus cycle length (SCL) was measured after 3, 5, and 10 Hz VSTIM before and after perfusion with ctx MII‐H9A;L15A (2020‐fold higher affinity for α6/β2 vs. α3/β2). Results At baseline VSTIM prolonged SCL by 345±38, 476±43, 901±125 msec. Perfusion with ctx MII‐H9A;L15A resulted in similar responses to VSTIM (300±29, 449±37, 866±125 msec, p>0.05, ANOVA) suggesting that blockade of α6/β2 did not alter responsiveness. Hexamethonium abolished responses to VSTIM confirming that the ganglion was perfused entirely by the cannulated sinus node artery. Conclusion The previously reported blockade in this ganglion by ctx MII is attributable specifically to α3/β2 nAChR and not α6 containing receptors.