Premium
Inhibition of Src kinase activity reduces heart rate with slight alteration of heart rate variability
Author(s) -
Jiang Jyun Hao,
Ho Jamie,
Phan Nhut Nam,
Tian Duong Thuy,
Do Thi Duyen,
Chang Howard,
Lin YenChang
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.706.1
Subject(s) - proto oncogene tyrosine protein kinase src , heart rate variability , medicine , heart rate , tyrosine kinase , endocrinology , tachycardia , kinase , phosphorylation , chemistry , cardiology , receptor , biochemistry , blood pressure
Heart rate variability (HRV) is the cardiac index representing the oscillation of the intervals between consecutive heartbeats (RR intervals in the ECG). It reflects the influences of the autonomic nervous system (ANS) on the sinus node. In order to investigate the involvement of tyrosine phosphorylation in cardiac function of the whole rat system and its effect on HRV, we employed a potent selective inhibitor of Src family kinases, PP2, to inhibit the activity of Src kinases that include Src, Fyn, and Yes. Heart rate was decreased 20% by PP2 at the dose of 0.2 mg/kg. PP3, a negative control compound of PP2, which does not inhibit the activity of Src kinases decreased heart rate by 8% (when at the identical dose of 0.2 mg/kg) when compared with the basal. Interestingly, HRV was not significantly altered at a relatively low dose of PP2 (0.2 mg/kg) when compared with that of PP3 or the basal. Unlike that of PP2, HRV was significantly decreased after application of 0.4 μg/kg isoproterenol. Similar to that of PP2, ZD7288, a specific inhibitor of Hyperpolarized Cyclic‐Nucleotide gated (HCN) pacemaker channels, when at the low dose of 0.2 mg/kg, was able to decrease the heart rate without significant change of HRV in comparison to isoproterenol. Overall, PP2, like ZD7288, can serve as a potential candidate in the treatment of tachycardia‐induced arrhythmias via inhibition of Src‐mediated tyrosine phosphorylation.