Premium
Insensitivity of cardiac delayed‐rectifier I Kr to tyrosine phosphorylation inhibitors and stimulators
Author(s) -
Missan Sergey,
Zhabyeyev Pavel,
Linsdell Paul,
McDonald Terence F
Publication year - 2006
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.0706776
Subject(s) - myocyte , tyrosine kinase , endocrinology , medicine , phosphorylation , genistein , patch clamp , tyrosine phosphorylation , tyrosine kinase inhibitor , platelet derived growth factor receptor , protein tyrosine phosphatase , sodium orthovanadate , inward rectifier potassium ion channel , biology , chemistry , growth factor , microbiology and biotechnology , receptor , ion channel , cancer
1 The rapidly activating delayed‐rectifying K + current ( I Kr ) in heart cells is an important determinant of repolarisation, and decreases in its density are implicated in acquired and inherited long QT syndromes. The objective of the present study on I Kr in guinea‐pig ventricular myocytes was to evaluate whether the current is acutely regulated by tyrosine phosphorylation. 2 Myocytes configured for ruptured‐patch or perforated‐patch voltage‐clamp were depolarised with 200‐ms steps to 0 mV for measurement of I Kr tail amplitude on repolarisations to −40 mV. 3 I Kr in both ruptured‐patch and perforated‐patch myocytes was only moderately (14–20%) decreased by 100 μ M concentrations of protein tyrosine kinase (PTK) inhibitors tyrphostin A23, tyrphostin A25, and genistein. However, similar‐sized decreases were induced by PTK‐inactive analogues tyrphostin A1 and daidzein, suggesting that they were unrelated to inhibition of PTK. 4 Ruptured‐patch and perforated‐patch myocytes were also treated with promoters of tyrosine phosphorylation, including phosphotyrosyl phosphatase (PTP) inhibitor orthovanadate, exogenous c‐Src PTK, and four receptor PTK activators (insulin, insulin‐like growth factor‐1, epidermal growth factor, and basic fibroblast growth factor). None of these treatments had a significant effect on the amplitude of I Kr . 5 We conclude that Kr channels in guinea‐pig ventricular myocytes are unlikely to be regulated by PTK and PTP.British Journal of Pharmacology (2006) 148 , 724–731. doi: 10.1038/sj.bjp.0706776