Endothelial cell signaling during conducted vasomotor responses

KA Dora, J Xia, BR Duling - American Journal of Physiology …, 2003 - journals.physiology.org
KA Dora, J Xia, BR Duling
American Journal of Physiology-Heart and Circulatory Physiology, 2003journals.physiology.org
ACh and KCl stimulate vasomotor responses that spread rapidly and bidirectionally along
arteriole walls, most likely via spread of electric current or Ca2+ through gap junctions. We
examined these possibilities with isolated, cannulated, and perfused hamster cheek pouch
arterioles (50-to 80-μm resting diameter). After intraluminal loading of 2 μM fluo 3 to
measure Ca2+ or 1 μM di-8-ANEPPS to measure membrane potential, photometric
techniques were used to selectively measure changes in intracellular Ca2+ concentration …
ACh and KCl stimulate vasomotor responses that spread rapidly and bidirectionally along arteriole walls, most likely via spread of electric current or Ca2+ through gap junctions. We examined these possibilities with isolated, cannulated, and perfused hamster cheek pouch arterioles (50- to 80-μm resting diameter). After intraluminal loading of 2 μM fluo 3 to measure Ca2+ or 1 μM di-8-ANEPPS to measure membrane potential, photometric techniques were used to selectively measure changes in intracellular Ca2+ concentration ([Ca2+]i) or membrane potential in endothelial cells. Activation of the endothelium by micropipette application of ACh (10-4 M, 1.0-s pulse) to a short segment of arteriole (100–200 μm) increased endothelial cell [Ca2+]i and caused hyperpolarization at the site of stimulation. This response was followed rapidly by vasodilation of the entire arteriole (∼2-mm length). Change in membrane potential always preceded dilation, both at the site of stimulation and at distant sites along the arteriole. In contrast, an increase in endothelial cell [Ca2+]i was observed only at the application site. Micropipette application of KCl, which can depolarize both smooth muscle and endothelial cells (250 mM, 2.5-s pulse), also caused a rapid, spreading response consisting of depolarization followed by vasoconstriction. With KCl stimulation, in addition to changes in membrane potential, increases in endothelial cell [Ca2+]i were observed at distant sites not directly exposed to KCl. The rapid longitudinal spread of both hyperpolarizing and depolarizing responses support electrical coupling as the mode of signal transmission along the arteriolar length. In addition, the relatively short distance between heterologous cell types enables the superimposed radial Ca2+ signaling between smooth muscle and endothelial cells to modulate vasomotor responses.
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