Histamine H3 receptor activation stimulates calcium mobilization in a subpopulation of rat striatal neurons in primary culture, but not in synaptosomes

Abstract

The histamine H₃ receptor (H₃R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H₃Rs couple to Gα_i/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 H₃R of 445 amino acids (hH₃R₄₄₅) results in phospholipase C (PLC) stimulation and release of Ca²⁺ from intracellular stores. In this work we have studied whether H₃R activation induces Ca²⁺ mobilization from intracellular stores in native systems, either isolated nerve terminals (synaptosomes) or neurons in primary culture. In rat striatal synaptosomes H₃R activation induced inositol 1,4,5-trisphosphate (IP₃) formation but failed to increase the intracellular calcium concentration ([Ca²⁺]_i). In striatal primary cultures H₃R 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 H₃R activation in a fraction of those cells that were responsive to membrane depolarization. These results indicate that H₃R activation stimulates the PLC/IP₃/Ca²⁺ pathway but only in a subpopulation of striatal neurons.

Keywords: Calcium mobilization; H(3) receptor; Histamine; Primary culture; Striatum; Synaptosomes.