Volatile anesthetic sensitivity of T-type calcium currents in various cell types.
We evaluated the effects of volatile anesthetics on T-type calcium current (ICa,T) present in four different cell types using the whole cell version of the patch clamp technique. In dorsal root ganglion neurons and in two neuroendocrine cells--adrenal glomerulosa cells (AG) and thyroid C-cells--ICa,T was reversibly decreased by volatile anesthetics at clinically relevant concentrations, with isoflurane and enflurane being more potent that halothane. In AG cells, the most sensitive cell type tested, ICa,T was reduced 47%+/-4% (n = 6) by isoflurane (0.7 mM) and 56%+/-2% (n = 5) by enflurane (1.2 mM), but by only 24%+/-1% (n = 5; P < 0.05) by halothane (0.7 mM). Isoflurane caused a significant increase in the rate of deactivation of ICa,T in AG cells. In ventricular myocytes, however, ICa,T was much less sensitive to both isoflurane and halothane. The differential sensitivity of ICa,T in various cell types to the anesthetics may reflect differences in the channels expressed in these tissues or differences in the cellular intermediates involved in anesthetic action. Depression of ICa,T in neuronal cells may contribute to anesthetic action through decreases in cellular excitability.


CONCLUSIONS
Using the patch clamp technique, we showed that T-type calcium channels, which promote cellular excitability, are inhibited by volatile anesthetics in neuronal and neuroendocrine cells, but not in ventricular myocytes. Inhibition of neuronal T-type channels may contribute to the mechanism of action of volatile anesthetics.
McDowell
T S
TS
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville, USA.
Pancrazio
J J
JJ
Barrett
P Q
PQ
Lynch
C
C
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012680:Sensitivity and Specificity; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D002118:Calcium