Nonselective ion pathways in human endothelial cells.
Four probably different transmembrane pathways are described in human endothelial (EN) cells that are all nonselective for cations. i) A nonselective cation channel that is more permeable for Na+ and K+ than for Ca2+ can be gated by agonists such as histamine. This channel provides an agonist-gated entry route for Ca2+ into EN cells with a single-channel conductance of 25 pS for Na+, K+, and approximately 4 pS for Ca2+ (110 mM). ii) Another Ca(2+)-permeable pathway can be activated by shear stress. This supposedly mechanically activated channel is more permeable for divalent than for monovalent cations and provides mechano-sensing properties to EN cells. iii) A third ionic current, activated by the selective Ca(2+)-ATPase blocker thapsigargin, seems to be related to Ca(2+)-release from Ca(2+)-stores in the endoplasmic reticulum. In EN cells, this Ca(2+)-entry route is cation selective, but cannot differentiate between Na+ and K+. Activation of this nonselective current is associated with an increase in intracellular Ca2+. We therefore assume a Ca(2+)-entry through this thapsigargin-activated pathway. iv) A nickel-blockable, Ca(2+)-permeable, nonselective leak is described that is present in nonstimulated EN cells. It will be discussed whether agonist-gated channels and leak channels might be related to the Ca(2+)-release activated Ca(2+)-entry mechanism.
Nilius
B
B
KU Leuven, Department of Physiology, Belgium.
Droogmans
G
G
Gericke
M
M
Schwarz
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009532:Nickel / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013314:Stress, Mechanical; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002412:Cations; D007473:Ion Channels; D014662:Vasoconstrictor Agents; D009532:Nickel; D006632:Histamine; D012964:Sodium; D011188:Potassium; D002118:Calcium