RGD Reference Report - Reciprocal modulation of I (h) and I (TASK) in thalamocortical relay neurons by halothane. - Rat Genome Database

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

Authors: Budde, T  Coulon, P  Pawlowski, M  Meuth, P  Kanyshkova, T  Japes, A  Meuth, SG  Pape, HC 
Citation: Budde T, etal., Pflugers Arch. 2008 Sep;456(6):1061-73. Epub 2008 May 14.
RGD ID: 2316619
Pubmed: PMID:18478257   (View Abstract at PubMed)
DOI: DOI:10.1007/s00424-008-0482-9   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hcn2Ratneuronal cell body  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hcn2  (hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2)


Additional Information