Reciprocal modulation of I (h) and I (TASK) in thalamocortical relay neurons by halothane

Pflugers Arch. 2008 Sep;456(6):1061-73. doi: 10.1007/s00424-008-0482-9. Epub 2008 May 14.


By combining electrophysiological, immunohistochemical, and computer modeling techniques, we examined the effects of halothane on the standing outward current (I (SO)) and the hyperpolarization-activated current (I (h)) in rat thalamocortical relay (TC) neurons of the dorsal lateral geniculate nucleus (dLGN). Hyperpolarizing voltage steps elicited an instantaneous current component (I (i)) followed by a slower time-dependent current that represented I (h). Halothane reduced I (h) by shifting the voltage dependency of activation toward more negative potentials and by reducing the maximal conductance. Moreover, halothane augmented I (i) and I (SO). During the blockade of I (h) through Cs+, the current-voltage relationship of the halothane-sensitive current closely resembled the properties of a current through members of the TWIK-related acid-sensitive K+ (TASK) channel family (I (TASK)). Computer simulations in a single-compartment TC neuron model demonstrated that the modulation of I (h) and I (TASK) is sufficient to explain the halothane-induced hyperpolarization of the membrane potential observed in current clamp recordings. Immunohistochemical staining revealed protein expression of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel proteins HCN1, HCN2, and HCN4. Together with the dual effect of halothane on I (h) properties, these results suggest that I (h) in TC neurons critically depends on HCN1/HCN2 heterodimers. It is concluded that the reciprocal modulation of I (h) and I (TASK) is an important mechanism of halothane action in the thalamus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / drug effects*
  • Computer Simulation
  • Cyclic Nucleotide-Gated Cation Channels / drug effects*
  • Electrophysiology
  • Extracellular Space / drug effects
  • Extracellular Space / physiology
  • Halothane / pharmacology*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Immunohistochemistry
  • Nerve Tissue Proteins
  • Neural Networks, Computer
  • Neural Pathways / cytology*
  • Neural Pathways / drug effects*
  • Neurons / drug effects*
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects*
  • Potassium Channels, Tandem Pore Domain / drug effects*
  • Rats
  • Rats, Long-Evans
  • Thalamus / cytology*
  • Thalamus / drug effects*


  • Anesthetics, Inhalation
  • Cyclic Nucleotide-Gated Cation Channels
  • Hcn1 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • potassium channel subfamily K member 3
  • Halothane