Ca2+ responses of pulmonary arterial myocytes to acute hypoxia require release from ryanodine and inositol trisphosphate receptors in sarcoplasmic reticulum.

American Journal of Physiology. Lung Cellular and Molecular Physiology
Jian WangJ T Sylvester

Abstract

In pulmonary arterial smooth muscle cells (PASMC), acute hypoxia increases intracellular Ca(2+) concentration ([Ca(2+)](i)) by inducing Ca(2+) release from the sarcoplasmic reticulum (SR) and Ca(2+) influx through store- and voltage-operated Ca(2+) channels in sarcolemma. To evaluate the mechanisms of hypoxic Ca(2+) release, we measured [Ca(2+)](i) with fluorescent microscopy in primary cultures of rat distal PASMC. In cells perfused with Ca(2+)-free Krebs Ringer bicarbonate solution (KRBS), brief exposures to caffeine (30 mM) and norepinephrine (300 μM), which activate SR ryanodine and inositol trisphosphate receptors (RyR, IP(3)R), respectively, or 4% O(2) caused rapid transient increases in [Ca(2+)](i), indicating intracellular Ca(2+) release. Preexposure of these cells to caffeine, norepinephrine, or the SR Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA; 10 μM) blocked subsequent Ca(2+) release to caffeine, norepinephrine, and hypoxia. The RyR antagonist ryanodine (10 μM) blocked Ca(2+) release to caffeine and hypoxia but not norepinephrine. The IP(3)R antagonist xestospongin C (XeC, 0.1 μM) blocked Ca(2+) release to norepinephrine and hypoxia but not caffeine. In PASMC perfused with normal KRBS, acute hypoxia caused a sus...Continue Reading

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Citations

Dec 4, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Vishal R YadavYong-Xiao Wang
Aug 12, 2014·Pharmacology & Therapeutics·Andrea OlschewskiHorst Olschewski
Oct 15, 2013·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Nikki L Jernigan, Thomas C Resta
Aug 21, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sebastián Castillo-GalánRoberto V Reyes
Nov 5, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Carlos H NittaNikki L Jernigan
Jul 29, 2017·Journal of Applied Physiology·Ievgen StrielkovNorbert Weissmann
Jun 19, 2013·The Journal of Physiology·Michelle J ConnollyPhilip I Aaronson

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