Calcium signaling in airway smooth muscle.
Contractility of airway smooth muscle requires elevation of intracellular calcium concentration. Under resting conditions, airway smooth muscle cells maintain a relatively low intracellular calcium concentration, and activation of the surface receptors by contractile agonists results in an elevation of intracellular calcium, culminating in contraction of the cell. The pattern of elevation of intracellular calcium brought about by agonists is a dynamic process and involves the coordinated activities of ion channels located in the plasma membrane and the sarcoplasmic reticulum. Among the signaling molecules involved in this dynamic calcium regulation in airway smooth muscle cells are inositol 1,4,5-trisphosphate and cyclic ADP-ribose, which mobilize calcium from the sarcoplasmic reticulum by acting via the inositol 1,4,5-trisphosphate and ryanodine receptors, respectively. In addition, calcium influx from the extracellular space is critical for the repletion of the intracellular calcium stores during activation of the cells by agonists. Calcium influx can occur via voltage- and receptor-gated channels in the plasma membrane, as well as by influx that is triggered by depletion of the intracellular stores (i.e., store-operated calcium entry mechanism). Transient receptor potential proteins appear to mediate the calcium influx via receptor- and store-operated channels. Recent studies have shown that proinflammatory cytokines regulate the expression and activity of the pathways involved in intracellular calcium regulation, thereby contributing to airway smooth muscle cell hyperresponsiveness. In this review, we will discuss the specific roles of cyclic ADP-ribose/ryanodine receptor channels and transient receptor potential channels in the regulation of intracellular calcium in airway smooth muscle cells.
Jude
Joseph A
JA
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA.
Wylam
Mark E
ME
Walseth
Timothy F
TF
Kannan
Mathur S
MS
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1 / Q000502:physiology; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D036563:Cyclic ADP-Ribose / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D016207:Cytokines; D036563:Cyclic ADP-Ribose; D015544:Inositol 1,4,5-Trisphosphate; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1