TY - JOUR
T1 - Effects of bepridil on stretch-activated BKca channels and stretch-induced extrasystoles in isolated chick hearts
AU - Jin, H.
AU - Iribe, Gentaro
AU - Naruse, K.
N1 - Funding Information:
This work was supported by the Japan Society for the Promotion of Sciences (JSPS KAKENHI: 23300167, 22136008, 22240056), Daiichi Sankyo Co., Ltd and National Natural Science Foundation of China (No. 81260035).
Publisher Copyright:
© 2017 Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
PY - 2017
Y1 - 2017
N2 - Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SACNS) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryonic ventricular myocytes were used for singlechannel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS, on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKca channels but possibly also blocks SACNS, and thus decreases the stretch-induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential).
AB - Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SACNS) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryonic ventricular myocytes were used for singlechannel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS, on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKca channels but possibly also blocks SACNS, and thus decreases the stretch-induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential).
KW - Arrhythmia
KW - Bepridil
KW - SAKca channels
KW - Stretch-activated channels
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U2 - 10.33549/physiolres.933315
DO - 10.33549/physiolres.933315
M3 - Article
C2 - 28248537
AN - SCOPUS:85026433046
SN - 0862-8408
VL - 66
SP - 459
EP - 465
JO - Physiological Research
JF - Physiological Research
IS - 3
ER -