PMID- 27777410 OWN - NLM STAT- MEDLINE DCOM- 20180430 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Oct 25 TI - Red blood cell thickness is evolutionarily constrained by slow, hemoglobin-restricted diffusion in cytoplasm. PG - 36018 LID - 10.1038/srep36018 [doi] LID - 36018 AB - During capillary transit, red blood cells (RBCs) must exchange large quantities of CO(2) and O(2) in typically less than one second, but the degree to which this is rate-limited by diffusion through cytoplasm is not known. Gas diffusivity is intuitively assumed to be fast and this would imply that the intracellular path-length, defined by RBC shape, is not a factor that could meaningfully compromise physiology. Here, we evaluated CO(2) diffusivity (D(CO2)) in RBCs and related our results to cell shape. D(CO2) inside RBCs was determined by fluorescence imaging of [H(+)] dynamics in cells under superfusion. This method is based on the principle that H(+) diffusion is facilitated by CO(2)/HCO(3)(-) buffer and thus provides a read-out of D(CO2). By imaging the spread of H(+) ions from a photochemically-activated source (6-nitroveratraldehyde), D(CO2) in human RBCs was calculated to be only 5% of the rate in water. Measurements on RBCs containing different hemoglobin concentrations demonstrated a halving of D(CO2) with every 75 g/L increase in mean corpuscular hemoglobin concentration (MCHC). Thus, to compensate for highly-restricted cytoplasmic diffusion, RBC thickness must be reduced as appropriate for its MCHC. This can explain the inverse relationship between MCHC and RBC thickness determined from >250 animal species. FAU - Richardson, Sarah L AU - Richardson SL AD - Department of Physiology, Anatomy and Genetics, Oxford OX1 3PT, European Union, United Kingdom. FAU - Swietach, Pawel AU - Swietach P AD - Department of Physiology, Anatomy and Genetics, Oxford OX1 3PT, European Union, United Kingdom. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161025 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Bicarbonates) RN - 0 (Hemoglobins) RN - 142M471B3J (Carbon Dioxide) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Bicarbonates/*blood MH - Biological Transport MH - Camelids, New World MH - Carbon Dioxide/*blood MH - Cell Shape/physiology MH - Chickens MH - Diffusion MH - Erythrocyte Indices/*physiology MH - Erythrocytes/*physiology MH - Hemoglobins/metabolism MH - Humans MH - Oxygen/blood MH - Pulmonary Gas Exchange/*physiology MH - Xenopus laevis PMC - PMC5078773 EDAT- 2016/10/26 06:00 MHDA- 2018/05/01 06:00 PMCR- 2016/10/25 CRDT- 2016/10/26 06:00 PHST- 2016/06/22 00:00 [received] PHST- 2016/10/11 00:00 [accepted] PHST- 2016/10/26 06:00 [pubmed] PHST- 2018/05/01 06:00 [medline] PHST- 2016/10/26 06:00 [entrez] PHST- 2016/10/25 00:00 [pmc-release] AID - srep36018 [pii] AID - 10.1038/srep36018 [doi] PST - epublish SO - Sci Rep. 2016 Oct 25;6:36018. doi: 10.1038/srep36018.