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Tertiapin‐Q removes a mechanosensitive component of muscarinic control of the sinoatrial pacemaker in the rat
Author(s) -
Han SuYoung,
Wilson Suzanne J,
Bolter Chris P
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05408.x
Subject(s) - muscarinic acetylcholine receptor , mechanosensitive channels , medicine , endocrinology , oxotremorine , acetylcholine , chemistry , stimulation , heart rate , atropine , receptor , blood pressure , ion channel
Summary 1. In an isolated right atrial preparation, an increase in right atrial pressure (RAP) produces an increase in atrial rate. This rate response is larger and occurs faster when there is background vagal or muscarinic stimulation. 2. We hypothesized that in the latter situation, an increase in RAP antagonizes the effect of muscarinic stimulation through stretch inactivation of the mechanosensitive muscarinic potassium current I K,ACh . 3. In two groups of bath‐mounted right atria isolated from male Wistar rats (control n = 12; 300 nmol/L tertiapin‐Q treated (to block I K,ACh ) n = 10), we examined the change in atrial rate when RAP was raised from 2 to 8 mmHg; oxotremorine‐M (oxo‐M; from 10 to 500 nmol/L) was added to incrementally activate muscarinic receptors. 4. In both control and tertiapin‐Q‐treated groups, oxo‐M reduced atrial rate, but its effect was less (∼40–50%) in the latter group ( P < 0.001). In control preparations, responses to an increase in RAP became progressively larger and quicker as the concentration of oxo‐M was increased, whereas in tertiapin‐Q treated preparations oxo‐M did not affect either the amplitude or the speed of the response ( P < 0.0001 for both). 5. The results support the hypothesis that atrial stretch antagonizes muscarinic slowing by its effect on I K,ACh . We suggest that through this mechanism, parasympathetic control of heart rate may be modulated continuously by RAP.