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

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