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 bg 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 mu m/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 navel 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.