H2 histamine receptor-phosphorylation of Kv3.2 modulates interneuron fast spiking.
Histamine-containing neurons of the tuberomammilary nucleus project to the hippocampal formation to innervate H1 and H2 receptors on both principal and inhibitory interneurons. Here we show that H2 receptor activation negatively modulates outward currents through Kv3.2-containing potassium channels by a mechanism involving PKA phosphorylation in inhibitory interneurons. PKA phosphorylation of Kv3.2 lowered the maximum firing frequency of inhibitory neurons, which in turn negatively modulated high-frequency population oscillations recorded in principal cell layers. All these effects were absent in a Kv3.2 knockout mouse. These data reveal a novel pathway for histamine-dependent regulation of high-frequency oscillations within the hippocampal formation.
Atzori
M
M
Laboratory of Cellular and Molecular Neurophysiology, NICHD, NIH, Rm. 5A72, Bldg. 49, Convent Drive, Bethesda, Maryland 20892, USA.
Lau
D
D
Tansey
E P
EP
Chow
A
A
Ozaita
A
A
Rudy
B
B
McBain
C J
CJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D017259:Dimaprit / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D010852:Picrotoxin / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*; D051670:Shaw Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology
D015056:1-Methyl-3-isobutylxanthine; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017259:Dimaprit; D009479:Neuropeptides; D010852:Picrotoxin; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011970:Receptors, Histamine H2; D051670:Shaw Potassium Channels; D019789:Tetraethylammonium