Insensitivity of cardiac delayed-rectifier I(Kr) to tyrosine phosphorylation inhibitors and stimulators.
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 microM 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.
Missan
Sergey
S
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
Zhabyeyev
Pavel
P
Linsdell
Paul
P
McDonald
Terence F
TF
D000818:Animals; D022062:Electrophysiologic Techniques, Cardiac; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000031:analogs & derivatives / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology*; D051669:Shab Potassium Channels / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
C496988:KCNB1 protein, human; D047428:Protein Kinase Inhibitors; D051669:Shab Potassium Channels; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases