关键词：
embryonic DRG neurons
histamine
H-1 receptor
cPLA(2)
arachidonic acid
K channels
摘要：
Histamine has been proposed to be an important modulator of developing neurons, but its mechanism of action remains unclear. In embryonic chick dorsal root ganglion neurons we found that histamine activates, through the pyrilamine-sensitive H-1 receptor, a K-selective, background channel. The K channel activated by histamine was also activated by arachidonic acid in a dose-dependent way, with a K-D of 4 muM and a slope of 2.5, had a unitary conductance of about 150 pS (symmetrical 140 KCI) and a moderate voltage dependence. The channel was insensitive to the classical K channel blockers tetraethylammonium, charybdotoxin, 4-aminopyridine, but inhibited by millimolar Ba2+. Channel activity could also be increased by lowering the intracellular pH from 7.2 to 5.5, or by applying negative pressure pulses through the patch pipette. Experiments aimed at delineating the metabotropic pathway leading to K channel activation by histamine indicated the involvement of a pertussis toxin-insensitive G protein, and a quinacrine-sensitive cytosolic phospholipase A(2). The histamine-induced K channel activation was observed only with elevated internal Ca2+ (achieved using 0.5 muM ionomycin or elevated external KCI). An increase in the histamine-induced phosphoinositide hydrolysis was also observed upon internal Ca2+ elevation, showing the presence of a Ca2+ dependent step upstream to inositol 1,4,5-triphosphate production. In view of the functional importance of K conductances during cell differentiation, we propose that histamine activation of this K channel may have a significant role during normal development of embryonic chick neurons. (C) 2004 Published by Elsevier Ltd on behalf of IBRO.
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