Ion channels and regulation of intracellular calcium in vascular endothelial cells

Abstract

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 Ca 2+ , which is caused by Ca 2+ entry via ion channels in the plasma membrane and by Ca 2+ release from intracellular stores. Ca 2+ entry may occur via four different mechanisms: 1 ) a receptor‐mediated channel coupled to second messengers; 2 ) a Ca 2+ leak channel dependent on the electrochemical gradient for Ca 2+ ; 3 ) a stretch‐activated nonselective cation channel; and 4 ) internal Na + ‐dependent Ca 2+ entry (Na + ‐Ca 2+ exchange). The rate of Ca 2+ 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 Ca 2+ ‐activated K channel activated upon depolarization, which may function to repolarize the agonist‐stimulated endothelial cell. After agonist stimulation, cytosolic Ca 2+ increases in a biphasic manner, with an initial peak due to inositol 1,4,5‐trisphosphate‐mediated Ca 2+ release from intracellular stores, followed by a sustained plateau that is dependent on the presence of [Ca 2+ ] o and on membrane potential. The delay in agonist‐activated Ca 2+ influx is consistent with the coupling of receptor activation to Ca 2+ entry via a second messenger. Oscillations in [Ca 2+ ] i , which may involve both Ca 2+ entry and release, have been observed in isolated and confluent endothelial cell monolayers stimulated by histamine and bradykinin. Receptor‐mediated Ca 2+ entry, release, and refilling of intracellular stores follows a cycle that involves the plasma membrane.—A dams , D. J.; B arakeh , J.; L askey , R.; V an B reemen , C. Ion channels and regulation of intracellular calcium in vascular endothelial cells. FASEB J. 3: 2389‐2400; 1989.