Local anesthetics inhibit the G protein-mediated modulation of K+ and Ca++ currents in anterior pituitary cells.

摘要

The effects of local anesthetics (LAs) on G protein-mediated responses of voltage-dependent K+ (I(K)) and Ca++ currents in rat anterior pituitary tumor (GH3) cells were analyzed by using a whole-cell voltage clamp. Extracellular lidocaine inhibited I(K) with an IC50 of 1.9 mM, comparable to 2.6 mM for I(Ba) but 10 times higher than the IC50 for I(Na) (0.17 mM). Low concentrations of lidocaine (30-100 microM), which had no direct effect on basal I(K), attenuated both the stimulatory and inhibitory modulation of K+ channels by thyrotropin-releasing hormone (TRH). Both modulations had an IC50 approximately 40 microM independent of [TRH]. Intracellular QX314 (100 microM), a quaternary, charged form of lidocaine, also significantly attenuated the TRH effects; however, external QX314 and the neutral LA benzocaine (100 microM) did not. Lidocaine (