Accentuated Antagonism in Vagal Heart Rate Control Mediated through Muscarinic Potassium Channels

DOI Web Site 被引用文献3件 参考文献36件
  • Mizuno Masaki
    Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute
  • Kamiya Atsunori
    Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute
  • Kawada Toru
    Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute
  • Miyamoto Tadayoshi
    Department of Physical Therapy, Faculty of Health Sciences, Morinomiya University of Medical Sciences
  • Shimizu Shuji
    Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute Japan Association for the Advancement of Medical Equipment
  • Shishido Toshiaki
    Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute
  • Sugimachi Masaru
    Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute

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Although muscarinic K+ (KACh) channels contribute to a rapid heart rate (HR) response to vagal stimulation, whether background sympathetic tone affects the HR control via the KACh channels remains to be elucidated. In seven anesthetized rabbits with sinoaortic denervation and vagotomy, we estimated the dynamic transfer function of the HR response by using random binary vagal stimulation (0–10 Hz). Tertiapin, a selective KACh channel blocker, decreased the dynamic gain (to 2.3 ± 0.9 beats·min–1·Hz–1, from 4.6 ± 1.1, P < 0.01, mean ± SD) and the corner frequency (to 0.05 ± 0.01 Hz, from 0.26 ± 0.04, P < 0.01). Under 5 Hz tonic cardiac sympathetic stimulation (CSS), tertiapin decreased the dynamic gain (to 3.6 ± 1.0 beats·min–1·Hz–1, from 7.3 ± 1.1, P < 0.01) and the corner frequency (to 0.06 ± 0.02 Hz, from 0.23 ± 0.06, P < 0.01). Two-way analysis of variance indicated significant interaction between the tertiapin and CSS effects on the dynamic gain. In contrast, no significant interactions were observed between the tertiapin and CSS effects on the corner frequency and the lag time. In conclusion, although a cyclic AMP-dependent mechanism has been well established, an accentuated antagonism also occurred in the direct effect of ACh via the KACh channels. The rapidity of the HR response obtained by the KACh channel pathway was robust during the accentuated antagonism. <br>

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