Open AccessContribution of Elevated Intracellular Calcium to Pulmonary Arterial Myocyte Alkalinization during Chronic Hypoxia
Author(s) -
Undem Clark,
Luke Trevor,
Shimoda Larissa A.
Publication year - 2016
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1086/685053
Subject(s) - intracellular ph , bepridil , extracellular , pulmonary hypertension , amiloride , hypoxia (environmental) , bicarbonate , calcium , medicine , contraction (grammar) , endocrinology , chemistry , hypoxic pulmonary vasoconstriction , intracellular , biophysics , biochemistry , sodium , biology , oxygen , verapamil , organic chemistry
In the lung, exposure to chronic hypoxia (CH) causes pulmonary hypertension, a debilitating disease. Development of this condition arises from increased muscularity and contraction of pulmonary vessels, associated with increases in pulmonary arterial smooth muscle cell (PASMC) intracellular pH (pH i ) and Ca 2+ concentration ([Ca 2+ ] i ). In this study, we explored the interaction between pH i and [Ca 2+ ] i in PASMCs from rats exposed to normoxia or CH (3 weeks, 10% O 2 ). PASMC pH i and [Ca 2+ ] i were measured with fluorescent microscopy and the dyes BCECF and Fura‐2. Both pH i and [Ca 2+ ] i levels were elevated in PASMCs from hypoxic rats. Exposure to KCl increased [Ca 2+ ] i and pH i to a similar extent in normoxic and hypoxic PASMCs. Conversely, removal of extracellular Ca 2+ or blockade of Ca 2+ entry with NiCl 2 or SKF 96365 decreased [Ca 2+ ] i and pH i only in hypoxic cells. Neither increasing pH i with NH 4 Cl nor decreasing pH i by removal of bicarbonate impacted PASMC [Ca 2+ ] i . We also examined the roles of Na + /Ca 2+ exchange (NCX) and Na + /H + exchange (NHE) in mediating the elevated basal [Ca 2+ ] i and Ca 2+ ‐dependent changes in PASMC pH i . Bepridil, dichlorobenzamil, and KB‐R7943, which are NCX inhibitors, decreased resting [Ca 2+ ] i and pH i only in hypoxic PASMCs and blocked the changes in pH i induced by altering [Ca 2+ ] i . Exposure to ethyl isopropyl amiloride, an NHE inhibitor, decreased resting pH i and prevented changes in pH i due to changing [Ca 2+ ] i . Our findings indicate that, during CH, the elevation in basal [Ca 2+ ] i may contribute to the alkaline shift in pH i in PASMCs, likely via mechanisms involving reverse‐mode NCX and NHE.