Thèse soutenue

Étude du comportement dynamique des canaux ioniques de la membrane du globule rouge humain
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Auteur / Autrice : Agnieszka Dyrda
Direction : Serge Thomas
Type : Thèse de doctorat
Discipline(s) : Biologie
Date : Soutenance en 2009
Etablissement(s) : Rennes 1
Ecole(s) doctorale(s) : École doctorale Vie-Agro-Santé (Rennes)
Partenaire(s) de recherche : autre partenaire : Université européenne de Bretagne (2007-2016)

Mots clés

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Résumé

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Erythrocytes are one of the cellular models frequently used to decipher the physiology of membrane transport. However, if pumps, antiporters and cotransporters are now well defined, the molecular identity and the physiological role of the conductive pathways present in the membrane of red blood cell (RBC) is still elusive albeit the growing evidences of their role in physiological and pathological conditions. The present work, using the patch clamp technique and biophysical studies, shows that: 1) The changes in osmotic fragility observed after Gardos channel dependent dehydration is mainly not due to rehydration of the cell via membrane transporters but rather due to change in membrane properties elicited by the Ca2+ loading. It reflects a specific calcium-induced lytic vulnerability of the membrane leading to rupture before the cells attain their maximal spherical volumes. 2) The Gardos channel can be transiently activated when seal formation induces membrane deformation. This phenomenon can result only from activation of a permeability pathway with a finite Ca2+ conductance. This transient activity generates secondary transient anionic channel activity that has been studied further. 3) The diversity of anionic channel activities recorded in normal human RBCs, as well as in P. Falciparum-infected RBCs, corresponds to different kinetic modalities of a unique type of maxi anion channel with multiple conductance levels, gating properties and pharmacology. Finally, the present work contributes to the understanding of the role of ion channels in RBCs and opens questions on the contribution of ion channels in the rheological properties of RBCs. Keywords: erythrocyte, ionic channels, osmotic fragility, patch clamp technique.