Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells

Background: Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Methods: Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH 3 ) cells were evaluated by patch clamp techniques. Results: ART inhibited the amplitude of delayed-rectifier K + current (I K(DR) ) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on I K(DR) with an IC 50 value of 11.2 µM and enhanced I K(DR) inactivation with a K D value of 14.7 µM. The steady-state inactivation curve of I K(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of I K(DR) in GH 3 cells. ART also decreased the peak amplitude of voltage-gated Na + current (I Na ) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late I Na , was effective at reversing ART-induced prolongation in inactivation time constant of I Na . Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Conclusion: Under ART exposure, the inhibitory actions on both I K(DR) and I Na could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo.