Volatile anesthetics reduce low-voltage-activated calcium currents in a 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 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 omega-conotoxin GVIA (omega-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 omega-CTX (400 nM) or nicardipine (1 microM) 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.
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville, USA.
T S
TS
McDowell
J J
JJ
Pancrazio
C
C
Lynch
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D004553:Electric Conductivity; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004737:Enflurane; D007530:Isoflurane; D002118:Calcium; D006221:Halothane