{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:11:24Z","timestamp":1789809084354,"version":"4.0.1"},"reference-count":38,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p> Moderate hemolytic anemia, abnormal erythrocyte morphology (spherocytosis), and decreased membrane stability are observed in mice with complete deficiency of all erythroid protein 4.1 protein isoforms (4.1<jats:sup>\u2212\/\u2212<\/jats:sup>; Shi TS et al. J Clin Invest 103: 331, 1999). We have examined the effects of erythroid protein 4.1 (4.1R) deficiency on erythrocyte cation transport and volume regulation. 4.1<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited erythrocyte dehydration that was associated with reduced cellular K and increased Na content. Increased Na permeability was observed in these mice, mostly mediated by Na\/H exchange with normal Na-K pump and Na-K-2Cl cotransport activities. The Na\/H exchange of 4.1<jats:sup>\u2212\/\u2212<\/jats:sup> erythrocytes was markedly activated by exposure to hypertonic conditions (18.2 \u00b1 3.2 in 4.1<jats:sup>\u2212\/\u2212<\/jats:sup> vs. 9.8 \u00b1 1.3 mmol\/10<jats:sup>13<\/jats:sup> cell \u00d7 h in control mice), with an abnormal dependence on osmolality (EC<jats:sub>50<\/jats:sub> = 417 \u00b1 42 in 4.1<jats:sup>\u2212\/\u2212<\/jats:sup> vs. 460 \u00b1 35 mosmol\/kgH<jats:sub>2<\/jats:sub>O in control mice), suggestive of an upregulated functional state. While the affinity for internal protons was not altered (K<jats:sub>0.5<\/jats:sub> = 489.7 \u00b1 0.7 vs. 537.0 \u00b1 0.56 nM in control mice), the V<jats:sub>max<\/jats:sub> of the H-induced Na\/H exchange activity was markedly elevated in 4.1<jats:sup>\u2212\/\u2212<\/jats:sup> erythrocytes ( V<jats:sub>max<\/jats:sub> 91.47 \u00b1 7.2 compared with 46.52 \u00b1 5.4 mmol\/10<jats:sup>13<\/jats:sup> cell \u00d7 h in control mice). Na\/H exchange activation by okadaic acid was absent in 4.1<jats:sup>\u2212\/\u2212<\/jats:sup> erythrocytes. Altogether, these results suggest that erythroid protein 4.1 plays a major role in volume regulation and physiologically downregulates Na\/H exchange in mouse erythrocytes. Upregulation of the Na\/H exchange is an important contributor to the elevated cell Na content of 4.1<jats:sup>\u2212\/\u2212<\/jats:sup> erythrocytes. <\/jats:p>","DOI":"10.1152\/ajpcell.00436.2005","type":"journal-article","created":{"date-parts":[[2006,6,15]],"date-time":"2006-06-15T00:49:50Z","timestamp":1150332590000},"page":"C880-C886","source":"Crossref","is-referenced-by-count":21,"title":["Effect of complete protein 4.1R deficiency on ion transport properties of murine erythrocytes"],"prefix":"10.1152","volume":"291","author":[{"given":"Alicia","family":"Rivera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"De Franceschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luanne L.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gascard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narla","family":"Mohandas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Brugnara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Armsby CC, Stuart-Tilley AK, Alper SL, and Brugnara C. 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