Inhibition of the activity of human lymphocyte Kv1.3 potassium channels by resveratrol.
The whole-cell patch-clamp technique was applied to study the modulatory effect of resveratrol on voltage-gated potassium channel Kv1.3 expressed in human lymphocytes. Results demonstrate that application of resveratrol in the concentration range 1-200 muM: inhibited the channel activity in a concentration-dependent manner to about 18% of the control value. The half-blocking concentration of resveratrol was 40.9 microM: , whereas the Hill coefficient was 1.05. The inhibition was time-dependent and slowly reversible. The inhibitory effect of resveratrol was correlated in time with a significant slowing of the current activation, whereas the inactivation rate remained unaffected upon application of resveratrol. The inhibition of Kv1.3 channels was voltage-independent. The steady-state activation of the currents remained unchanged upon resveratrol application. The magnitude of the inhibitory effect of resveratrol was not altered when resveratrol was coapplied with genistein. The possible mechanism of the inhibitory effect and its significance for biological activity of resveratrol are discussed.
Teisseyre
Andrzej
A
Department of Biophysics, Wrocław Medical University, ul. Chałubińskiego 10, 50-368, Wrocław, Poland. ateiss@biofiz.am.wroc.pl
Michalak
Krystyna
K
D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D051664:Kv1.3 Potassium Channel; D013267:Stilbenes; D019833:Genistein; D000077185:Resveratrol