Analysis of the chronotropic effect of acetylcholine on sinoatrial node cells

被引:66
作者
Zhang, HG
Holden, AV
Noble, D
Boyett, MR [1 ]
机构
[1] Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England
[2] Univ Oxford, Physiol Lab, Oxford OX1 3PT, England
[3] UMIST, Dept Phys, Biol Phys Grp, Manchester M60 1QD, Lancs, England
关键词
sinus node; pacemaker; pacemaker shift; mathematical modeling;
D O I
10.1046/j.1540-8167.2002.00465.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 X 10(-8) and 14 X 10(-8) M ACh, respectively, caused a 50% decrease in pacemaking rate, whereas in rabbit SA node similar to7.4 X 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).
引用
收藏
页码:465 / 474
页数:10
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