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Analysis of the Chronotropic Effect of Acetylcholine on Sinoatrial Node Cells
Author(s) -
ZHANG HENGGUI,
HOLDEN ARUN V.,
NOBLE DENIS,
BOYETT MARK R.
Publication year - 2002
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2002.00465.x
Subject(s) - chronotropic , acetylcholine , sinoatrial node , medicine , peripheral , endocrinology , muscarinic acetylcholine receptor , heart rate , pharmacology , cardiology , receptor , blood pressure
Analysis of Chronotropic Effect of ACh.Introduction: The ionic basis underlying the negative chronotropic effect of acetylcholine (ACh) on sinoatrial (SA) node cells is unresolved and controversial. In the present study, mathematical modeling was used to address this issue. Methods and Results: The known concentration‐dependent effects of ACh on i K,ACh , i Ca,L , and i f were introduced into models of rabbit central and peripheral SA node cells. In the central and peripheral models, 9 × 10 −8 and 14 × 10 −8 M ACh , respectively, caused a 50% decrease in pacemaking rate, whereas in rabbit SA node ˜ 7.4 × 10 −8 M ACh caused such a decrease. In the models, i K,ACh was primarily responsible for the decrease and actions of ACh on i Ca,L or i f alone caused a negligible effect. Although the inhibition of i f did not directly contribute to the chronotropic effect, it was indirectly important, because it minimized the opposition by i f to the decrease of rate caused by activation of i K,ACh . The central model was more sensitive to ACh than the peripheral model. Conclusion: The chronotropic effect of ACh is principally the result of activation of i K,ACh , and inhibition of i Ca,L plays little or no role. Inhibition of i f and possible inhibition of i b,Na play an important facilitative role by reducing the ability of i f and i b,Na to curtail the chronotropic effect caused by activation of i K,ACh .