Stimulatory Actions of Thymol, a Natural Product, on Ca²⁺-Activated K⁺ Current in Pituitary GH₃ Cells

Abstract

Drugs that influence the opening of potassium (K⁺) channels and as a consequence cause hyperpolarization of cell membrane possess clinical potential. The large conductance Ca²⁺-activated K⁺ (BK) channel is highly selective for K⁺. Activation of this channel is Ca²⁺- and voltage-dependent. We have investigated the effects of thymol, a natural product, on ion currents in pituitary GH₃ cells. The patch-clamp technique was used to investigate the effect of thymol (100 μM) in these cells. Thymol reversibly stimulated the Ca²⁺-activated K⁺ current with an EC₅₀ value of 75 μM. 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 μM) nor zingerone (100 μM) had an effect on BK-channel activity while AAPH (100 μM) suppressed it significantly. The stimulatory actions of thymol on Ca²⁺-activated K⁺ currents may be associated with the underlying cellular mechanisms through which it affects neuronal or neuroendocrine functions.

Thymol - Ca²⁺-activated K⁺ current - large-conductance Ca²⁺-activated K⁺ channel - GH₃ cells

References

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