Ion channels and regulation of intracellular calcium in vascular endothelial cells.
Endothelial cells in vivo form an interface between flowing blood and vascular tissue, responding to humoral and physical stimuli to secrete relaxing and contracting factors that contribute to vascular homeostasis and tone. The activation of endothelial cell-surface receptors by vasoactive agents is coupled to an elevation in cytosolic Ca2+, which is caused by Ca2+ entry via ion channels in the plasma membrane and by Ca2+ release from intracellular stores. Ca2+ entry may occur via four different mechanisms: 1) a receptor-mediated channel coupled to second messengers; 2) a Ca2+ leak channel dependent on the electrochemical gradient for Ca2+; 3) a stretch-activated nonselective cation channel; and 4) internal Na+-dependent Ca2+ entry (Na+-Ca2+ exchange). The rate of Ca2+ entry through these ion pathways can be modulated by the resting membrane potential. Membrane potential may be regulated by at least two types of K channels: inwardly rectifying K channels activated upon hyperpolarization or shear stress; and a Ca2+-activated K channel activated upon depolarization, which may function to repolarize the agonist-stimulated endothelial cell. After agonist stimulation, cytosolic Ca2+ increases in a biphasic manner, with an initial peak due to inositol 1,4,5-trisphosphate-mediated Ca2+ release from intracellular stores, followed by a sustained plateau that is dependent on the presence of [Ca2+]o and on membrane potential. The delay in agonist-activated Ca2+ influx is consistent with the coupling of receptor activation to Ca2+ entry via a second messenger. Oscillations in [Ca2+]i, which may involve both Ca2+ entry and release, have been observed in isolated and confluent endothelial cell monolayers stimulated by histamine and bradykinin. Receptor-mediated Ca2+ entry, release, and refilling of intracellular stores follows a cycle that involves the plasma membrane.
Adams
D J
DJ
Department of Pharmacology, University of Miami School of Medicine, Florida 33101.
Barakeh
J
J
Laskey
R
R
Van Breemen
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D009569:Nitric Oxide / Q000378:metabolism
D007473:Ion Channels; D009569:Nitric Oxide; D011464:Epoprostenol; D002118:Calcium