Persistent histamine excitation of glutamatergic preoptic neurons.
Thermoregulatory neurons of the median preoptic nucleus (MnPO) represent a target at which histamine modulates body temperature. The mechanism by which histamine excites a population of MnPO neurons is not known. In this study it was found that histamine activated a cationic inward current and increased the intracellular Ca(2+) concentration, actions that had a transient component as well as a sustained one that lasted for tens of minutes after removal of the agonist. The sustained component was blocked by TRPC channel blockers. Single-cell reverse transcription-PCR analysis revealed expression of TRPC1, TRPC5 and TRPC7 subunits in neurons excited by histamine. These studies also established the presence of transcripts for the glutamatergic marker Vglut2 and for the H1 histamine receptor in neurons excited by histamine. Intracellular application of antibodies directed against cytoplasmic sites of the TRPC1 or TRPC5 channel subunits decreased the histamine-induced inward current. The persistent inward current and elevation in intracellular Ca(2+) concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca(2+) elevation in glutamatergic MnPO neurons.
The Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California, USA. tabarean@scripps.edu
Iustin V
IV
Tabarean
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D011301:Preoptic Area / Q000187:drug effects* / Q000502:physiology*; D011738:Pyrilamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism; D014311:Triprolidine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; C493477:Slc17a6 protein, mouse; D050052:TRPC Cation Channels; D050599:Vesicular Glutamate Transport Protein 2; D005973:Glutamine; D014311:Triprolidine; D006632:Histamine; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D011738:Pyrilamine; D002118:Calcium