Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm


Grahn E, Kaufmann SV, Askarova M, Ninov M, Welp LM, Berger TK, Urlaub H, Kaupp UB


Nature Communications


Nat Commun. 2023 Sep 5;14(1):5395.


The reaction of CO2 with H2O to form bicarbonate (HCO3) and H+ controls sperm motility and fertilization via HCO3-stimulated cAMP synthesis. A complex network of signaling proteins participates in this reaction. Here, we identify key players that regulate intracellular pH (pHi) and HCO3 in human sperm by quantitative mass spectrometry (MS) and kinetic patch-clamp fluorometry. The resting pH2 is set by amiloride-sensitive Na+/H+ exchange. The sperm-specific putative Na+/H+ exchanger SLC9C1, unlike its sea urchin homologue, is not gated by voltage or cAMP. Transporters and channels implied in HCO3 transport are not detected, and may be present at copy numbers < 10 molecules/sperm cell. Instead, HCO3 is produced by diffusion of CO2 into cells and readjustment of the CO2/HCO3/H+ equilibrium. The proton channel Hv1 may serve as a unidirectional valve that blunts the acidification ensuing from HCO3 synthesis. This work provides a new framework for the study of male infertility.


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