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.
McDowell
T S
TS
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville, USA.
Pancrazio
J J
JJ
Lynch
C
C
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