VOLATILE ANESTHETICS REDUCE LOW-VOLTAGE-ACTIVATED CALCIUM CURRENTS INA THYROID C-CELL LINE

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 examine d. Methods: Whole-cell calcium currents were recorded using standard p atch clamp techniques. Current-voltage relationships were derived befo re, during, and after application of isoflurane, enflurane, or halotha ne. 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 omega-conot oxin GVIA (omega-CTX) and nicardipine. Results: All three agents rever sibly decreased both LVA and HVA currents at clinically relevant conce ntrations. 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 cu rrents to a similar extent: -22 +/- 4% versus -29 +/- 3% for 0.65 mM h alothane (n = 6). Isoflurane had no effect on LVA whole-cell current k inetics. Pretreatment with either omega-CTX (400 nM) or nicardipine (1 mu M) did not change the sensitivity of HVA current to isoflurane. Co nclusions: Isoflurane and enflurane block LVA calcium channels more po tently than either L-type or N-type calcium channels, but halothane sh ows no such preferential effect. These results may have implications f or the mechanism action of volatile anesthetics.