Histamine-activated, non-selective cation currents and Ca2+ transients in endothelial cells from human umbilical vein.
Permeation properties and modulation of an ionic current gated by histamine were measured in single endothelial cells from human umbilical cord veins by use of the patch-clamp technique in the ruptured-whole-cell mode or using perforated patches. We combined these current measurements with a microfluorimetric method to measure concomitantly free intracellular calcium concentration ([Ca2+]i). Application of histamine induced an intracellular calcium transient and an ionic current that reversed near 0 mV. The amplitude of the current ranged from -0.2 to -2 nA at -100 mV. The tonic rise in [Ca2+]i and the ionic current are partly due to Ca2+ influx. This Ca2+ entry pathway is also permeable for Ba2+ and Mn2+. The amplitude of the histamine-activated current was also closely correlated with the amplitude of the concomitant Ca2+ transient, suggesting that the latter is at least partially due to Ca2+ influx through histamine-activated channels. The reversal potential of the histamine-induced current was 7.6 +/- 4.1 mV (n = 14) when the calcium concentration in the bath solution ([Ca2+]o) was 1.5 mmol/l. With 10 mmol/l [Ca2+]o it was -13.7 +/- 4.7 mV and shifted to + 13.0 +/- 1.5 mV in nominally Ca(2+)-free solution (n = 3 cells). The amplitude of the current in Ca(2+)-free solution was enhanced compared to that in 10 mmol/l [Ca2+]o. The shift of the reversal potential and the concomitant change of the current amplitude suggest that the channel is permeable for calcium but has a smaller permeability for calcium than for monovalent cations.(ABSTRACT TRUNCATED AT 250 WORDS)
Nilius
B
B
Max Planck Group Molecular and Cellular Physiology, K. U. Leuven, Belgium.
Schwartz
G
G
Oike
M
M
Droogmans
G
G
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009761:Nystatin / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D002413:Cations, Divalent; D007473:Ion Channels; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D009761:Nystatin; D006632:Histamine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C