Volatile anesthetic sensitivity of T-type calcium currents in various cell types

We evaluated the effects of volatile anesthetics on T-type calcium current (I-Ca,I-T) present in four different cell types using the whole cell version of the patch clamp technique. Ln dorsal root ganglion neurons and in two neuroendocrine cells-adrenal glomerulosa cells (AG) and thyroid C-cells-I-Ca,I-T was reversibly decreased by volatile anesthetics at clinically relevant concentrations, with isoflurane and enflurane being more potent that halothane. Ln AG cells, the most sensitive cell type tested, I-Ca,I-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% +/- 3% (n = 5; P < 0.05) by halothane (0.7 mM). Isoflurane caused a significant increase in the rate of deactivation of I-Ca,I-T in AG cells. In ventricular myocytes, however, I-Ca,I-T was much less sensitive to both isoflurane and halothane. The differential sensitivity of I-Ca,I-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 I-Ca,I-T in neuronal cells may contribute to anesthetic action through decreases in cellular excitability. Implications: Using the patch clamp technique, we showed that T-h;Fe 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.