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

• DOI: 10.1111/apha.14205
• Publication Date: 2024-07-19T12:20:09Z
• Authors: Till S. Harter; Emma A. Smith; Cristina Salmerón; Angus B. Thies; Bryan Delgado; Rod W. Wilson; Martin Tresguerres
• Keywords: Intracellular pH; Acid–base homeostasis

Abstract Aim To identify the physiological role of acid‐base sensing enzyme, soluble adenylyl cyclase (sAC), in red blood cells (RBC) model teleost fish, rainbow trout. Methods We used: (i) super‐resolution microscopy to determine subcellular location sAC protein; (ii) live‐cell imaging RBC intracellular pH (pH i ) with specific inhibition (KH7 or LRE1) its cellular regulation; (iii) spectrophotometric measurements haemoglobin–oxygen (Hb‐O 2 binding steady‐state conditions; and (iv) during simulated arterial‐venous transit, systemic O transport. Results Distinct pools protein were detected cytoplasm, at plasma membrane within nucleus. Inhibition decreased setpoint for regulation by ~0.25 units compared controls, slowed rates recovery after an disturbance. was entirely through anion exchanger (AE) that part regulated HCO 3 − ‐dependent signaling. Hb‐O affinity a respiratory acidosis controls reduced cooperativity binding. During vitro simulations amount is unloaded ~11%. Conclusion represents novel sensor RBCs trout, where it participates modulation transport though AE activity. If substantiated other species, these findings may have broad implications our understanding cardiovascular physiology vertebrates.