Ca2+ waves in lung capillary endothelium.
Although cytosolic Ca2+ importantly regulates organ function, lung microvascular [Ca2+]i regulation remains poorly understood because of the lack of direct in situ quantification. In the present study, we report the first endothelial [Ca2+]i quantification by the fura 2 method in microscopically imaged venular capillaries of the isolated blood-perfused rat lung. Sequential images indicated the presence of intercellular Ca2+ waves that spontaneously originated from pacemaker endothelial cells and then spread for short distances along the capillary wall, inducing synchronous endothelial [Ca2+]i oscillations. Fast Fourier analyses of the oscillations revealed a dominant wave component with an amplitude of 37 nmol/L, frequency of 0.4 min-1, and velocity of 5 microns/s. The intracellular Ca2+ wave was unaffected by blood flow stoppage or by infusions of Ca(2+)-containing or Ca(2+)-free dextran. Inhibition of the wave by thapsigargin in Ca(2+)-free dextran and by the gap junction uncoupler, heptanol, indicated that it was generated by endosomal Ca2+ release in the pacemaker cell and was propagated by gap junctional communication. In the presence of histamine, enhancement of the wave accounted for a significant component of the coordinated [Ca2+]i increase in the capillary segment. No intercellular Ca2+ waves were evident in adjoining alveolar epithelial cells. Our findings indicate a novel mechanism of [Ca2+]i regulation in the lung capillary under both resting and stimulated conditions. Pacemaker-induced Ca2+ waves, generated intracellularly by unknown initiating mechanisms, communicated to adjoining cells to determine [Ca2+]i profiles in short interbranch segments of capillary walls.
Ying
X
X
Department of Medicine, College of Physicians & Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York, NY 10019, USA.
Minamiya
Y
Y
Fu
C
C
Bhattacharya
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D008168:Lung / Q000098:blood supply*; D008833:Microcirculation / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002118:Calcium