Histamine H 3 receptor activation stimulates calcium mobilization in a subpopulation of rat striatal neurons in primary culture, but not in synaptosomes.

The histamine H3 receptor (H3 R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H3 Rs couple to Gαi/o proteins and trigger or modulate several intracellular signaling pathways, including the cAMP/PKA pathway and the opening of N- and P/Q-type voltage-gated Ca2+ channels. In transfected cells, activation of the human H3 R of 445 amino acids (hH3 R445 ) results in phospholipase C (PLC) stimulation and release of Ca2+ from intracellular stores. In this work we have studied whether H3 R activation induces Ca2+ mobilization from intracellular stores in native systems, either isolated nerve terminals (synaptosomes) or neurons in primary culture. In rat striatal synaptosomes H3 R activation induced inositol 1,4,5-trisphosphate (IP3 ) formation but failed to increase the intracellular calcium concentration ([Ca2+ ]i ). In striatal primary cultures H3 R activation resulted in IP3 formation and increased the [Ca2+ ]i in 18 out of 70 cells that responded with an elevation in the [Ca2+ ]i to membrane depolarization with KCl (100 mM) as evaluated by microfluorometry. Confocal microscopy studies corroborated the increase in [Ca2+ ]i induced by H3 R activation in a fraction of those cells that were responsive to membrane depolarization. These results indicate that H3 R activation stimulates the PLC/IP3 /Ca2+ pathway but only in a subpopulation of striatal neurons.