Genistein inhibits the activity of kv1.3 potassium channels in human T lymphocytes

• Published in: The Journal of membrane biology 2005-05, Vol.205 (2), p.71-79
• Main Authors: Teisseyre, A, Michalak, K
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Dose-Response Relationship, Drug; Genistein - pharmacology; Humans; In Vitro Techniques; Kv1.3 Potassium Channel - antagonists & inhibitors; Membrane Potentials - drug effects; Patch-Clamp Techniques; Potassium Channel Blockers - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism
• ISSN: 0022-2631; 1432-1424
• DOI: 10.1007/s00232-005-0764-5

In the present study, the whole-cell patch-clamp technique was applied to follow the inhibitory effect of genistein--a tyrosine kinase inhibitor and a natural anticancer agent--on the activity of voltage-gated potassium channels Kv1.3 expressed in human T lymphocytes (TL). Obtained data provide evidence that genistein application in the concentration range of 1-80 microM reversibly decreased the whole-cell potassium currents in TL in a concentration-dependent manner to about 0.23 of the control value. The half-blocking concentration range of genistein was from 10 to 40 microM. The current inhibition was correlated in time with a significant decrease of the current activation rate. The steady-state activation of the currents was unchanged upon application of genistein, as was the inactivation rate. The inhibitory effect of genistein on the current amplitude and activation kinetics was voltage-independent. The current inhibition was not changed significantly in the presence of 1 mM of sodium orthovanadate, a tyrosine phosphatase inhibitor. Application of daidzein, an inactive genistein analogue, did not affect significantly either the current amplitudes or the activation kinetics. Possible mechanisms of the observed phenomena and their significance for genistein-induced inhibition of cancer cell proliferation are discussed.