The effects of halothane on single human neuronal L-type calcium channels.
We investigated halothane's effects on the function of L-type Ca2+ channels in a human neuronal cell line, SH-SY5Y, by using the cell-attached patch voltage clamp configuration and Ba2+ as the charge carrier. In multiple-channel patches, halothane decreased the peak and persistent Ba2+ currents, accelerated the rate of inactivation, and slowed the rate of activation. Single-channel analysis showed that halothane (0.14-1.26 mM) increased the latency time for the first channel opening, increased the lifetime of nonconducting events, increased the proportion of short-lived open events, decreased the lifetime of the two open populations, and increased the percentage of current traces without channel activity. All of the observed halothane effects contribute to the halothane-induced decrease in macroscopic Ba2+ currents. The halothane concentration producing 50% reduction (IC50) of the peak Ba2+ current was 0.80 mM (approximately 1.9 hypothetical minimum alveolar anesthetic concentration [H-MAC] at 28 degrees C) and of the persistent Ba2+ current was 0.69 mM (approximately 1.7 H-MAC). The halothane effects did not always occur together, and the Hill slope of 1.6 suggested the presence of more than one interaction site or of more than one population of L-type Ca2+ channels. Halothane reduces L-type Ca2+ channel currents in human neuronal cells primarily through the stabilization of nonconducting states such as closed (before and after channel opening) and inactivated states.


CONCLUSIONS
Calcium is a signaling molecule in neurons. We measured the effect of halothane on Ba2+ (a Ca2+ surrogate) movement into a human neuron-like cell electronically. Ba2+ entry through the L-type channel was depressed. Halothane decreased the likelihood of the channel opening and enhanced the rate at which the channel closed and inactivated. These actions of halothane are probably related to its anesthetic action.
Nikonorov
I M
IM
Department of Anesthesiology, The Hospital for Special Surgery, New York, New York 10021, USA.
Blanck
T J
TJ
Recio-Pinto
E
E
D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004563:Electrochemistry; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D014407:Tumor Cells, Cultured
D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D001464:Barium; D006221:Halothane