Nonselective ion pathways in human endothelial cells

• Published in: EXS (Basel) Vol. 66; p. 269
• Main Authors: Nilius, B, Droogmans, G, Gericke, M, Schwarz, G
• Format: Journal Article
• Language: English
• Published: Switzerland 1993
• Subjects: Animals; Calcium - metabolism; Cations - metabolism; Endothelium, Vascular - physiology; Histamine - pharmacology; Humans; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Ion Channels - drug effects; Ion Channels - physiology; Membrane Potentials - drug effects; Models, Biological; Nickel - pharmacology; Potassium - metabolism; Sodium - metabolism; Stress, Mechanical; Vasoconstrictor Agents - pharmacology
• ISSN: 1023-294X
• DOI: 10.1007/978-3-0348-7327-7_21

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.