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GENERAL ARTICLES

Volatile Anesthetic Sensitivity of T-Type Calcium Currents in Various Cell Types

Thomas S. McDowell, MD, PhD^*, Joseph J. Pancrazio, PhD^*,, Paula Q. Barrett, PhD, and Carl Lynch, III, MD, PhD^*

Departments of *Anesthesiology, Biomedical Engineering, and Pharmacology, University of Virginia Health Sciences Center, Charlottesville, Virginia

Address correspondence and reprint requests to Thomas S. McDowell, MD, PhD, Department of Anesthesiology, B6/319 CSC, University of Wisconsin Hospital, 600 Highland Ave., Madison, WI 53792-3272.

We evaluated the effects of volatile anesthetics on T-type calcium current (I_Ca,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—I_Ca,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, I_Ca,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 I_Ca,T in AG cells. In ventricular myocytes, however, I_Ca,T was much less sensitive to both isoflurane and halothane. The differential sensitivity of I_Ca,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,T in neuronal cells may contribute to anesthetic action through decreases in cellular excitability.

Implications: 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.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999