Volatile anesthetic sensitivity of T-type calcium currents in various celltypes

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 versio n of the patch clamp technique. Ln dorsal root ganglion neurons and in two neuroendocrine cells-adrenal glomerulosa cells (AG) and thyroid C-cells-I-C a,I-T was reversibly decreased by volatile anesthetics at clinically releva nt concentrations, with isoflurane and enflurane being more potent that hal othane. Ln AG cells, the most sensitive cell type tested, I-Ca,I-T was redu ced 47% +/- 4% (n = 6) by isoflurane (0.7 mM) and 56% +/- 2% (n = 5) by enf lurane (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 muc h less sensitive to both isoflurane and halothane. The differential sensiti vity of I-Ca,I-T in various cell types to the anesthetics may reflect diffe rences in the channels expressed in these tissues or differences in the cel lular intermediates involved in anesthetic action. Depression of I-Ca,I-T i n neuronal cells may contribute to anesthetic action through decreases in c ellular excitability. Implications: Using the patch clamp technique, we sho wed 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 co ntribute to the mechanism of action of volatile anesthetics.