ISSN:
1540-8167
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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 iK,ACh, iCa,L, and if 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, iK,ACh was primarily responsible for the decrease and actions of ACh on iCa,L or if alone caused a negligible effect. Although the inhibition of if did not directly contribute to the chronotropic effect, it was indirectly important, because it minimized the opposition by if to the decrease of rate caused by activation of iK,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 iK,ACh, and inhibition of iCa,L plays little or no role. Inhibition of if and possible inhibition of ib,Na play an important facilitative role by reducing the ability of if and ib,Na to curtail the chronotropic effect caused by activation of iK,ACh.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1540-8167.2002.00465.x
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