Reciprocal modulation of I (h) and I (TASK) in thalamocortical relay neurons by halothane.
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.
Budde
Thomas
T
Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Robert-Koch-Str. 27a, 48149, Münster, Germany. tbudde@uni-muenster.de
Coulon
Philippe
P
Pawlowski
Matthias
M
Meuth
Patrick
P
Kanyshkova
Tatyana
T
Japes
Ansgar
A
Meuth
Sven G
SG
Pape
Hans-Christian
HC
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects*; D003198:Computer Simulation; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects*; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D006221:Halothane / Q000494:pharmacology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins; D016571:Neural Networks, Computer; D009434:Neural Pathways / Q000166:cytology* / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D013788:Thalamus / Q000166:cytology* / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D054815:Cyclic Nucleotide-Gated Cation Channels; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D006221:Halothane