Volatile anesthetics reduce low-voltage-activated calcium currents in a thyroid C-cell line

Abstract

Background: Volatile anesthetics may act in part by inhibiting voltage- dependent calcium channels. The effects of several volatile agents on three types of calcium channels in a thyroid C-cell line were examined. Methods: Whole-cell calcium currents were recorded using standard patch clamp techniques. Current-voltage relationships were derived before, during, and after application of isoflurane, enflurane, or halothane. Low-voltage- activated (LVA; T type) calcium currents were isolated based on the voltage range of activation. High-voltage-activated (HVA) calcium currents were separated into L and N types using ω-conotoxin GVIA (ω-CTX) and nicardipine. Results: All three agents reversibly decreased both LVA and HVA currents at clinically relevant concentrations. Isoflurane and enflurane both reduced peak LVA current more than peak HVA current: -33 ± 6% (mean ± SE) versus -22 ± 4% for 0.71 mM isoflurane (n = 6), and -46 ± 6% versus -35 ± 5% for 1.21 mM enflurane (n = 6). In contrast, halothane depressed LVA and HVA currents to a similar extent: -22 ± 4% versus -29 ± 3% for 0.65 mM halothane (n = 6). Isoflurane had no effect on LVA whole-cell current kinetics. Pretreatment with either ω-CTX (400 nM) or nicardipine (1 μM) did not change the sensitivity of HVA current to isoflurane. Conclusions. Isoflurane and enflurane block LVA calcium channels more potently than either L-type or N-type calcium channels, but halothane shows no such preferential effect. These results may have implications for the mechanism action of volatile anesthetics.