Inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in rat supraoptic neurons: Involvement in histamine-induced enhancement of depolarizing afterpotentials

Histamine, a putative neuromodulator and neurotransmitter, can depolarize s upraoptic neurons and enhance depolarizing afterpotentials that play a key role in determining the excitability of these neurons. This study investiga ted intracellular signal transduction involved in histamine-induced enhance ment of depolarizing afterpotentials utilizing immunohistochemical and elec trophysiological methods. Abundant inositol 1,4,5-trisphosphate receptor-re lated immunostaining was seen in all parts of the supraoptic nucleus, mainl y within somata and proximal processes of the magnocellular neurons, but al so in astrocytes of the ventral glial lamina. In supraoptic neurons display ing depolarizing afterpotentials, three brief depolarizations evoked a slow inward current. Bath application of histamine (1-2.5 mu M) reversibly enha nced this slow inward current in almost all supraoptic neurons tested. Ampl itudes and durations of the slow inward current were increased by 68.1% and 22.8%, respectively. Pretreatment of cells with a histamine receptor (subt ype 1) antagonist (pyrilamine) or inhibitors of phospholipase C activation (neomycin or U73122) prevented histamine-induced enhancement of the slow in ward current. When electrodes containing heparin, an inositol 1,4,5-trispho sphate receptor blocker, were used for recording, histamine had no effect o n the slow inward current. Heparin, however, failed to abolish norepinephri ne-induced enhancement of the slow inward current. After H-7 [1-(5-isoquino linylsulfonyl)-2-methylpiperazine], an inhibitor of protein kinase C, was i nfused into supraoptic neurons via the electrodes, histamine-induced enhanc ement of the slow inward current was also blocked. These results indicate the presence of, and:functional roles for, inositol 1,4,5-trispbosphate receptor-sensitive Ca2+ stores in supraoptic neurons. F ollowing activation of histamine receptors (subtype 1) and phospholipase C, Ca2+ mobilization from internal stores participates in mediating histamine -induced enhancement of depolarizing afterpotentials. (C) 1999 IBRO. publis hed by Elsevier Science Ltd.