ECB-ART-52480
Nat Commun
2023 Sep 05;141:5395. doi: 10.1038/s41467-023-40855-0.
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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
.
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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 pHi 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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