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 supraoptic neurons and enhance depolarizing afterpotentials that play a key role in determining the excitability of these neurons. This study investigated intracellular signal transduction involved in histamine-induced enhancement of depolarizing afterpotentials utilizing immunohistochemical and electrophysiological methods. Abundant inositol 1,4,5-trisphosphate receptor-related immunostaining was seen in all parts of the supraoptic nucleus, mainly within somata and proximal processes of the magnocellular neurons, but also in astrocytes of the ventral glial lamina. In supraoptic neurons displaying depolarizing afterpotentials, three brief depolarizations evoked a slow inward current. Bath application of histamine (1-2.5 microM) reversibly enhanced this slow inward current in almost all supraoptic neurons tested. Amplitudes and durations of the slow inward current were increased by 68.1% and 22.8%, respectively. Pretreatment of cells with a histamine receptor (subtype 1) antagonist (pyrilamine) or inhibitors of phospholipase C activation (neomycin or U73122) prevented histamine-induced enhancement of the slow inward current. When electrodes containing heparin, an inositol 1,4,5-trisphosphate receptor blocker, were used for recording, histamine had no effect on the slow inward current. Heparin, however, failed to abolish norepinephrine-induced enhancement of the slow inward current. After H7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], an inhibitor of protein kinase C, was infused into supraoptic neurons via the electrodes, histamine-induced enhancement of the slow inward current was also blocked. These results indicate the presence of, and functional roles for, inositol 1,4,5-trisphosphate receptor-sensitive Ca2+ stores in supraoptic neurons. Following activation of histamine receptors (subtype 1) and phospholipase C, Ca2+ mobilization from internal stores participates in mediating histamine-induced enhancement of depolarizing afterpotentials.
Li
Z
Z
Department of Neuroscience, University of California at Riverside, 92521, USA.
Miyata
S
S
Hatton
G I
GI
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D007150:Immunohistochemistry; D007293:Inosine Triphosphate / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D007293:Inosine Triphosphate; D006632:Histamine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium; D009638:Norepinephrine