Stimulatory actions of thymol, a natural product, on Ca(2+)-activated K(+) current in pituitary GH(3) cells

Drugs that influence the opening of potassium (K(+)) channels and as a consequence cause hyperpolarization of cell membrane possess clinical potential. The large conductance CA(2+)-activated K(+) (BK) channel is highly selective for K(+). Activation of this channel is CA(2+)- and voltage-dependent. We have investigated the effects of thymol, a natural product, on ion currents in pituitary GH(3) cells. The patch-clamp technique was used to investigate the effect of thymol (100 microM) in these cells. Thymol reversibly stimulated the CA(2+)-activated K(+) current with an EC (50) value of 75 microM. In a cell-attached configuration, application of thymol to the bath increased the activity of BK channels. BAPTA (1 mM) attenuated thymol-stimulated channel activity. In an experiment using the inside-out configuration, thymol exposed to the intracellular face of excised patches did not modify the single-channel conductance of these channels whereas it enhanced the channel activity. Neither menthol (100 microM) nor zingerone (100 microM) had an effect on BK-channel activity while AAPH (100 microM) suppressed it significantly. The stimulatory actions of thymol on CA(2+)-activated K(+) currents may be associated with the underlying cellular mechanisms through which it affects neuronal or neuroendocrine functions.