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Groschner, K; Graier, WF; Kukovetz, WR.
Histamine induces K+, Ca2+, and Cl- currents in human vascular endothelial cells. Role of ionic currents in stimulation of nitric oxide biosynthesis.
Circ Res. 1994; 75(2):304-314 Doi: 10.1161/01.RES.75.2.304 [OPEN ACCESS]
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Leading authors Med Uni Graz: Groschner Klaus
Co-authors Med Uni Graz: Graier Wolfgang
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Abstract:: The nature of the membrane currents mediating agonist-induced Ca2+ entry and enhanced nitric oxide (NO) production in endothelial cells is still unclear. Using both perforated-patch and conventional whole-cell clamp technique, we have studied the membrane response associated with histamine stimulation of human vascular endothelial cells. In perforated-patch experiments, the initial histamine (10 mumol/L)-induced current reversed close to the K+ equilibrium potential and was blocked by tetrabutylammonium ions (TBA, 10 mmol/L). In addition, a TBA-insensitive current that developed slowly in the presence of histamine was recorded. This delayed histamine-induced current reversed close to neutral potential and was inhibited by SK&F 96365 (25 mumol/L), a putative blocker of receptor-operated Ca2+ channels. Similar histamine effects were observed in conventional whole-cell experiments using pipette solutions with low Ca(2+)-buffering capacity. Strong buffering of intracellular free Ca2+ suppressed the initial, but not the delayed, current response. The delayed component of histamine-induced current was substantially inhibited by the Cl- channel blocker N-phenylanthranilic acid (NPA, 100 mumol/L), and an eightfold change in the Cl- gradient shifted the reversal potential of this current by 30 mV. In Cl(-)-free solutions, histamine induced an SK&F 96365-sensitive NPA-resistant current, which, according to reversal potential measurements in 20 mmol/L extracellular Ca2+, corresponded to a cation conductance with 13- to 25-fold selectivity for Ca2+ over K+. Both SK&F 96365 and TBA strongly suppressed histamine-induced rises in intracellular free Ca2+ and cellular cGMP levels, whereas NPA did not. Our results provide the first demonstration that three distinct ionic conductances contribute to the histamine-induced membrane response of endothelial cells. It is suggested that histamine induces a Cl- conductance that is apparently not involved in Ca2+ homeostasis and regulation of NO biosynthesis, while, in parallel, joint activation of a rapidly induced K+ permeability and a slowly developing cation permeability mediate Ca2+ entry and stimulation of endothelial NO production.
Find related publications in this database (using NLM MeSH Indexing): Anthranilic Acids - pharmacology; Calcium - physiology; Cells, Cultured -; Chlorides - physiology; Electrophysiology -; Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Endothelium, Vascular - physiology; Histamine - pharmacology; Humans -; Imidazoles - pharmacology; Ions -; Nitric Oxide - biosynthesis; Potassium - physiology; Quaternary Ammonium Compounds - pharmacology
Find related publications in this database (Keywords): ENDOTHELIAL CELLS; PATCH CLAMP; CA2+ ENTRY; ENDOTHELIUM-DERIVED RELAXING FACTOR NITRIC OXIDE