| Autor: |
Kaestner L; Theoretical Medicine and Biosciences, Saarland University, Homburg, Germany. lars_kaestner@me.com.; Experimental Physics, Saarland University, Saarbrücken, Germany. lars_kaestner@me.com., Bogdanova A; Red Blood Cell Research Group, Institute of Veterinary Physiology, Vetsuisse Faculty and the Zürich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland., Egee S; CNRS, UMR8227 LBI2M, Sorbonne Université, Roscoff, France.; Laboratoire d'Excellence GR-Ex, Paris, France. |
| Jazyk: |
angličtina |
| Zdroj: |
Advances in experimental medicine and biology [Adv Exp Med Biol] 2020; Vol. 1131, pp. 625-648. |
| DOI: |
10.1007/978-3-030-12457-1_25 |
| Abstrakt: |
Free Calcium (Ca 2+ ) is an important and universal signalling entity in all cells, red blood cells included. Although mature mammalian red blood cells are believed to not contain organelles as Ca 2+ stores such as the endoplasmic reticulum or mitochondria, a 20,000-fold gradient based on a intracellular Ca 2+ concentration of approximately 60 nM vs. an extracellular concentration of 1.2 mM makes Ca 2+ -permeable channels a major signalling tool of red blood cells. However, the internal Ca 2+ concentration is tightly controlled, regulated and maintained primarily by the Ca 2+ pumps PMCA1 and PMCA4. Within the last two decades it became evident that an increased intracellular Ca 2+ is associated with red blood cell clearance in the spleen and promotes red blood cell aggregability and clot formation. In contrast to this rather uncontrolled deadly Ca 2+ signals only recently it became evident, that a temporal increase in intracellular Ca 2+ can also have positive effects such as the modulation of the red blood cells O 2 binding properties or even be vital for brief transient cellular volume adaptation when passing constrictions like small capillaries or slits in the spleen. Here we give an overview of Ca 2+ channels and Ca 2+ -regulated channels in red blood cells, namely the Gárdos channel, the non-selective voltage dependent cation channel, Piezo1, the NMDA receptor, VDAC, TRPC channels, Ca V 2.1, a Ca 2+ -inhibited channel novel to red blood cells and i.a. relate these channels to the molecular unknown sickle cell disease conductance P sickle . Particular attention is given to correlation of functional measurements with molecular entities as well as the physiological and pathophysiological function of these channels. This view is in constant progress and in particular the understanding of the interaction of several ion channels in a physiological context just started. This includes on the one hand channelopathies, where a mutation of the ion channel is the direct cause of the disease, like Hereditary Xerocytosis and the Gárdos Channelopathy. On the other hand it applies to red blood cell related diseases where an altered channel activity is a secondary effect like in sickle cell disease or thalassemia. Also these secondary effects should receive medical and pharmacologic attention because they can be crucial when it comes to the life-threatening symptoms of the disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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