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Does tyrosine kinase modulate delayed-rectifier K channels in guinea pig ventricular cells?
T Washizuka1, M Horie, K Obayashi
1Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan.
Heart and Vessels
|January 1, 1997
Summary
Genistein, a tyrosine kinase inhibitor, was found to inhibit cardiac potassium currents (IK). This effect was observed even though other tyrosine kinase inhibitors did not impact IK, suggesting a non-tyrosine kinase mechanism.
Area of Science:
- Cardiovascular Physiology
- Molecular Pharmacology
- Ion Channel Function
Background:
- Tyrosine kinase phosphorylation influences cellular growth, hypertrophy, and ion channel modulation.
- Cardiac delayed-rectifier potassium currents (IK) are crucial for cardiac repolarization.
Purpose of the Study:
- To investigate the effects of genistein, a protein tyrosine kinase (PTK) inhibitor, on cardiac IK.
- To determine if genistein's effect on IK is mediated through PTK inhibition.
Main Methods:
- Utilized guinea pig ventricular myocytes in a whole-cell voltage-clamp configuration.
- Measured tail and steady-state IK amplitudes under basal, hypotonic swelling-enhanced, and cyclic adenosine monophosphate (cAMP)-enhanced conditions.
- Tested genistein, daidzein (inactive analog), lavendustin A, and tyrphostin 51 at various concentrations.
Main Results:
- Genistein (10-100 microM) reversibly inhibited basal, swelling-enhanced, and cAMP-enhanced IK in a concentration-dependent manner.
- Daidzein also affected cAMP-enhanced IK, indicating a potential non-specific effect.
- Other PTK inhibitors, lavendustin A and tyrphostin 51, did not affect IK.
Conclusions:
- Genistein inhibits cardiac delayed-rectifier potassium currents (IK).
- The inhibitory effect of genistein on IK is likely not mediated by the inhibition of tyrosine kinase activity.