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The bee venom peptide tertiapin underlines the role of I KACh in acetylcholine‐induced atrioventricular blocks
Author(s) -
Drici MilouDaniel,
Diochot Sylvie,
Terrenoire Cécile,
Romey Georges,
Lazdunski Michel
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703611
Subject(s) - acetylcholine , chronotropic , medicine , atropine , anti arrhythmia agents , pharmacology , potassium channel , vagus nerve , cardiology , chemistry , heart rate , stimulation , atrial fibrillation , blood pressure
Acetylcholine (ACh) is an important neuromodulator of cardiac function that is released upon stimulation of the vagus nerve. Despite numerous reports on activation of I KACh by acetylcholine in cardiomyocytes, it has yet to be demonstrated what role this channel plays in cardiac conduction. We studied the effect of tertiapin, a bee venom peptide blocking I KACh , to evaluate the role of I KACh in Langendorff preparations challenged with ACh. ACh (0.5 μ M ) reproducibly and reversibly induced complete atrioventricular (AV) blocks in retroperfused guinea‐pig isolated hearts ( n =12). Tertiapin (10 to 300 n M ) dose‐dependently and reversibly prevented the AV conduction decrements and the complete blocks in unpaced hearts ( n =8, P <0.01). Tertiapin dose‐dependently blunted the ACh‐induced negative chronotropic response from an ACh‐induced decrease in heart rate of 39±16% in control conditions to 3±3% after 300 n M tertiapin ( P =0.01). These effects were not accompanied by any significant change in QT intervals. Tertiapin blocked I KACh with an IC 50 of 30±4 n M with no significant effect on the major currents classically associated with cardiac repolarisation process ( I Kr , I Ks , I to1 , I sus , I K1 or I KATP ) or AV conduction ( I Na and I Ca(L) ). In summary, tertiapin prevents dose‐dependently ACh‐induced AV blocks in mammalian hearts by inhibiting I KACh .British Journal of Pharmacology (2000) 131 , 569–577; doi: 10.1038/sj.bjp.0703611