TY - JOUR
T1 - Accentuated antagonism in vagal heart rate control mediated through muscarinic potassium channels
AU - Mizuno, Masaki
AU - Kamiya, Atsunori
AU - Kawada, Toru
AU - Miyamoto, Tadayoshi
AU - Shimizu, Shuji
AU - Shishido, Toshiaki
AU - Sugimachi, Masaru
PY - 2008/12
Y1 - 2008/12
N2 - 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 K ACh 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.
AB - 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 K ACh 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.
KW - Accentuated antagonism
KW - Muscarinic receptor
KW - Rabbit
KW - Sympathovagal interaction
KW - Systems analysis
KW - Transfer function
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U2 - 10.2170/physiolsci.RP011508
DO - 10.2170/physiolsci.RP011508
M3 - Article
C2 - 18842163
AN - SCOPUS:57749116329
SN - 1880-6546
VL - 58
SP - 381
EP - 388
JO - Journal of Physiological Sciences
JF - Journal of Physiological Sciences
IS - 6
ER -