© 1996 American Heart Association, Inc.
Articles |
Ca2+ Waves in Lung Capillary Endothelium
the Departments of Medicine and Physiology & Cellular Biophysics, College of Physicians & Surgeons, Columbia University, St. Luke's–Roosevelt Hospital Center, New York, NY.
Correspondence to Dr Jahar Bhattacharya, Columbia University College of Physicians & Surgeons, St. Luke's–Roosevelt Hospital Center, 1000 10th Ave, New York, NY 10019. E-mail jb39@columbia.edu.
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 µm/s. The intracellular Ca2+ wave was unaffected by blood flow stoppage or by infusions of Ca2+-containing or Ca2+-free dextran. Inhibition of the wave by thapsigargin in Ca2+-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.
Key Words: pulmonary microcirculation • rat • Ca2+ oscillation • endothelium • histamine
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