Depolarization modulates endothelial cell calcium influx and microvessel permeability.
We investigated the mechanisms whereby high-potassium (57.9 mM) Ringer solutions attenuate the increase in permeability caused when microvessels are exposed to the calcium ionophores ionomycin and A23187 (5 microM). In single perfused microvessels we measured cytoplasmic calcium concentration, [Ca2+]i, in the cells forming the microvessel wall and the hydraulic conductivity, Lp, to follow changes in the permeability of the microvessel walls. In normal Ringer solution, [Ca2+]i was increased to an initial peak value of 226 +/- 12 nM after exposure to calcium ionophores; the corresponding increase in microvessel Lp was 10.3 +/- 2.6 times control. With high-potassium solutions, the peak value of [Ca2+]i was 133 +/- 12 nM and Lp was increased to only 2.5 +/- 0.7 times control. Increasing extracellular calcium from 1.1 to 5 mM with high potassium restored the initial peak value of [Ca2+]i to 303 +/- 38 nM. The increases in both [Ca2+]i and Lp were abolished in calcium-free solutions. If high-potassium solutions depolarize the cells forming the microvessel wall as indicated by the membrane potential-sensitive dye bisoxonol, then the magnitude of the initial increase in [Ca2+]i could be accounted for by changes in the electrochemical driving force through conductive channels for calcium ion. Our results conform to the hypothesis that the permeability properties of microvessels are modulated by changes in the membrane potential of the endothelial cells and/or pericytes forming the microvessel wall.
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Department of Human Physiology, School of Medicine, University of California, Davis 95616.
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D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002199:Capillary Permeability; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D008833:Microcirculation; D009532:Nickel / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011894:Rana pipiens; D000077331:Ringer's Solution; D013997:Time Factors
D007552:Isotonic Solutions; D000001:Calcimycin; D015759:Ionomycin; D009532:Nickel; D000077331:Ringer's Solution; D011188:Potassium; D002118:Calcium