In vivo red blood cell sickling and mechanism of recovery in whiting, Merlangius merlangus

The Journal of Experimental Biology
Pia Koldkjaer, Michael Berenbrink

Abstract

Haemoglobin concentrations in vertebrate red blood cells are so high that in human sickle cell disease a single surface amino acid mutation can result in formation of large insoluble haemoglobin aggregates at low oxygen levels, causing peculiar cell deformations or 'sickling'. This may cause vascular occlusion and thereby severe pain, organ failure and death. Here, using light and transmission electron microscopy, we demonstrate extensive in vivo sickling of whiting red blood cells after capture stress without any apparent haemolysis and show its subsequent recovery. We show exceptionally high cooperative proton binding during the sickling process in vitro and identify the reduction of extracellular pH below resting values as the primary cause for in vivo sickling, although the response is modulated to a lesser extent also by oxygen tension. Using isotope tracer fluxes, we further show that beta-adrenergic hormones, which are released under capture stress, activate a powerful endogenous Na/H exchanger in these fish red blood cells, which is known to elevate intracellular pH. beta-adrenergic treatment further leads to a marked reduction of acid-induced in vitro sickling, which is impaired when Na/H exchange is inhibited by amilo...Continue Reading

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Citations

Feb 22, 2011·Proteins·Mitra S Rana, Austen F Riggs
Jul 20, 2018·Experimental Physiology·Benjamin ChatelDavid Bendahan
Sep 13, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Pia KoldkjaerMichael Berenbrink
May 31, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Roy E WeberThomas A Gorr

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