Abstract
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 Ca2+ 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 Ca2+ concentration could be reversed by activating the PKA pathway. This data reveal a novel mechanism by which histamine induces persistent excitation and sustained intracellular Ca2+ elevation in glutamatergic MnPO neurons.
Highlights
Histamine controls arousal, attention, feeding and thermoregulation
In a previous study we have identified two distinct mechanisms by which histamine modulates the activity of median preoptic nucleus (MnPO) neurons and core body temperature: inhibition of GABAergic neurons expressing H3 receptors and excitation of non-GABAergic neurons expressing H1 receptors [10]
The present study investigates the ionic mechanisms of histamine depolarization of identified glutamatergic MnPO neurons and the role of TRPC channels in these actions
Summary
Attention, feeding and thermoregulation (reviewed in [1]). In a previous study we have identified two distinct mechanisms by which histamine modulates the activity of MnPO neurons and core body temperature: inhibition of GABAergic neurons expressing H3 receptors and excitation of non-GABAergic neurons expressing H1 receptors [10]. We have further determined that histamine decreases the firing rate of GABAergic neurons by augmenting an A-type current conducted by Kv4.2-containing channels [6]. The ionic mechanism involved in the depolarization induced by H1 receptor activation is not known. The present study investigates the ionic mechanisms of histamine depolarization of identified glutamatergic MnPO neurons and the role of TRPC channels in these actions
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