Soluble adenylyl cyclase is an acid-base sensor in rainbow trout red blood cells that regulates intracellular pH and haemoglobin-oxygen binding.

Autor: Harter TS; Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA., Smith EA; Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA., Salmerón C; Department of Pharmacology, University of California San Diego, La Jolla, California, USA., Thies AB; Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA., Delgado B; Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA., Wilson RW; Biosciences Department, College of Life and Environmental Sciences, University of Exeter, Exeter, UK., Tresguerres M; Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2024 Oct; Vol. 240 (10), pp. e14205. Date of Electronic Publication: 2024 Jul 19.
DOI: 10.1111/apha.14205
Abstrakt: Aim: To identify the physiological role of the acid-base sensing enzyme, soluble adenylyl cyclase (sAC), in red blood cells (RBC) of the model teleost fish, rainbow trout.
Methods: We used: (i) super-resolution microscopy to determine the subcellular location of sAC protein; (ii) live-cell imaging of RBC intracellular pH (pH i ) with specific sAC inhibition (KH7 or LRE1) to determine its role in cellular acid-base regulation; (iii) spectrophotometric measurements of haemoglobin-oxygen (Hb-O 2 ) binding in steady-state conditions; and (iv) during simulated arterial-venous transit, to determine the role of sAC in systemic O 2 transport.
Results: Distinct pools of sAC protein were detected in the RBC cytoplasm, at the plasma membrane and within the nucleus. Inhibition of sAC decreased the setpoint for RBC pH i regulation by ~0.25 pH units compared to controls, and slowed the rates of RBC pH i recovery after an acid-base disturbance. RBC pH i recovery was entirely through the anion exchanger (AE) that was in part regulated by HCO 3 - -dependent sAC signaling. Inhibition of sAC decreased Hb-O 2 affinity during a respiratory acidosis compared to controls and reduced the cooperativity of O 2 binding. During in vitro simulations of arterial-venous transit, sAC inhibition decreased the amount of O 2 that is unloaded by ~11%.
Conclusion: sAC represents a novel acid-base sensor in the RBCs of rainbow trout, where it participates in the modulation of RBC pH i and blood O 2 transport though the regulation of AE activity. If substantiated in other species, these findings may have broad implications for our understanding of cardiovascular physiology in vertebrates.
(© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
Databáze: MEDLINE
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