Expression of a functional hyperpolarization-activated current (Ih) in the mouse nucleus reticularis thalami.
The GABAergic neurons of the nucleus reticularis thalami (nRT) express the type 2 hyperpolarization-activated cAMP-sensitive (HCN2) subunit mRNA, but surprisingly, they were reported to lack the hyperpolarization-activated (Ih) current carried by this subunit. Using the voltage-clamp recordings in the thalamocortical slice preparation of the newborn and juvenile mice (P6-P23), we demonstrate that, in the presence of 1 mM barium (Ba2+), the nRT neurons express a slow hyperpolarization-activated inward current, suggesting that the Ih is present but masked in control conditions by K+ leak currents. We investigate the identity of the hyperpolarization-activated current in the nRT by studying its physiological and pharmacological profile in presence of Ba2+. We show that it has voltage- and time-dependent properties typical of the Ih, that it is blocked by cesium and ZD7288, two blockers of the Ih, and that it is carried both by the K+ and Na+ ions. We could also alter the gating characteristics of the hyperpolarization-activated current in the nRT by adding a nonhydrolysable analogue of cAMP to the pipette solution. Finally, using the current-clamp recording, we showed that blocking the hyperpolarization-activated current induced an hyperpolarization correlated with an increase of the R(in) of the nRT neurons. In conclusion, our results demonstrate that the nRT neurons express the Ih with slow kinetics similar to those described for the homomeric HCN2 channels, and we show that the Ih of the nRT contributes to the excitability of the nRT neurons in normal conditions.
Rateau
Y
Y
Laboratoire de Neurophysiologie et Nouvelles Microscopies, Institut National de la Santé et de la Recherche Médicale U603, Université Paris Descartes, Paris, France.
Ropert
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D020644:Midline Thalamic Nuclei / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
C578711:Hcn2 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D011743:Pyrimidines; D026941:Sodium Channel Blockers; C082246:ICI D2788; D002586:Cesium; D015124:8-Bromo Cyclic Adenosine Monophosphate; D001464:Barium; D013779:Tetrodotoxin; D012964:Sodium; D011188:Potassium