Abstract
Free Calcium (Ca2+) 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 Ca2+ stores such as the endoplasmic reticulum or mitochondria, a 20,000-fold gradient based on a intracellular Ca2+ concentration of approximately 60 nM vs. an extracellular concentration of 1.2 mM makes Ca2+-permeable channels a major signalling tool of red blood cells. However, the internal Ca2+ concentration is tightly controlled, regulated and maintained primarily by the Ca2+ pumps PMCA1 and PMCA4. Within the last two decades it became evident that an increased intracellular Ca2+ 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 Ca2+ signals only recently it became evident, that a temporal increase in intracellular Ca2+ can also have positive effects such as the modulation of the red blood cells O2 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 Ca2+ channels and Ca2+-regulated channels in red blood cells, namely the Gárdos channel, the non-selective voltage dependent cation channel, Piezo1, the NMDA receptor, VDAC, TRPC channels, CaV2.1, a Ca2+-inhibited channel novel to red blood cells and i.a. relate these channels to the molecular unknown sickle cell disease conductance Psickle. 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.
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References
Berridge MJ (1994) The biology and medicine of calcium signalling. Mol Cell Endocrinol 98:119–124
Berridge MJ (2006) Calcium microdomains: organization and function. Cell Calcium 40:405–412
Bogdanova A, Makhro A, Wang J et al (2013) Calcium in red blood cells-a perilous balance. Int J Mol Sci 14:9848–9872. https://doi.org/10.3390/ijms14059848
Lew VL, Tsien RY, Miner C, Bookchin RM (1982) Physiological [Ca2+]i level and pump-leak turnover in intact red cells measured using an incorporated Ca chelator. Nature 298:478–481
Danielczok JG, Terriac E, Hertz L et al (2017) Red blood cell passage of small capillaries is associated with transient Ca2+-mediated adaptations. Front Physiol 8:979. https://doi.org/10.3389/fphys.2017.00979
Hammer K, Ruppenthal S, Viero C et al (2010) Remodelling of Ca2+ handling organelles in adult rat ventricular myocytes during long term culture. J Mol Cell Cardiol 49:427–437. https://doi.org/10.1016/j.yjmcc.2010.05.010
Schatzmann HJ (1983) The red cell calcium pump. Annu Rev Physiol 45:303–312. https://doi.org/10.1146/annurev.ph.45.030183.001511
Scharff O, Foder B (1977) Low Ca2+ concentrations controlling two kinetic states of Ca2+-ATPase from human erythrocytes. Biochim Biophys Acta 483:416–424
Kosk-Kosicka D, Bzdega T (1990) Effects of calmodulin on erythrocyte Ca2(+)-ATPase activation and oligomerization. Biochemistry 29:3772–3777
Wang KK, Roufogalis BD, Villalobo A (1990) Calpain I activates Ca2+ transport by the human erythrocyte plasma membrane calcium pump. Adv Exp Med Biol 269:175–180
Wang KK, Villalobo A, Roufogalis BD (1992) The plasma membrane calcium pump: a multiregulated transporter. Trends Cell Biol 2:46–52
Kosk-Kosicka D, Bzdega T (1988) Activation of the erythrocyte Ca2+-ATPase by either self-association or interaction with calmodulin. J Biol Chem 263:18184–18189
Andrews DA, Low PS (1999) Role of red blood cells in thrombosis. Curr Opin Hematol 6:76–82
Kaestner L, Tabellion W, Lipp P, Bernhardt I (2004) Prostaglandin E2 activates channel-mediated calcium entry in human erythrocytes: an indication for a blood clot formation supporting process. Thromb Haemost 92:1269–1272. https://doi.org/10.1267/THRO04061269
Lang KS, Duranton C, Poehlmann H et al (2003) Cation channels trigger apoptotic death of erythrocytes. Cell Death Differ 10:249–256. https://doi.org/10.1038/sj.cdd.4401144
Kaestner L, Minetti G (2017) The potential of erythrocytes as cellular aging models. Cell Death Differ 24:1475–1477. https://doi.org/10.1038/cdd.2017.100
Lang KS, Lang PA, Bauer C et al (2005) Mechanisms of suicidal erythrocyte death. Cell Physiol Biochem 15:195–202
Galluzzi L, Vitale I, Aaronson SA et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ:1–56. https://doi.org/10.1038/s41418-017-0012-4
Makhro A, Hanggi P, Goede JS et al (2013) N-methyl D-aspartate (NMDA) receptors in human erythroid precursor cells and in circulating red blood cells contribute to the intracellular calcium regulation. Am J Physiol Cell Physiol. https://doi.org/10.1152/ajpcell.00031.2013
Cahalan SM, Lukacs V, Ranade SS et al (2015) Piezo1 links mechanical forces to red blood cell volume. Elife 4:e07370. https://doi.org/10.7554/eLife.07370
Faucherre A, Kissa K, Nargeot J et al (2014) Piezo1 plays a role in erythrocyte volume homeostasis. Haematologica 99:70–75. https://doi.org/10.3324/haematol.2013.086090
Hamill OP (1983) Potassium and chloride channels in red blood cells. In: Sakmann B, Neher E (eds) Single channel recording. Plenum Press, New York/London, pp 451–471
Hamill OP (1981) Potassium channel currents in human red blood cells. J Physiol Lond 319:97P–98P
Gardos G (1956) The permeability of human erythrocytes to potassium. Acta Physiol Hung 10:185–189
Gardos G (1958) The function of calcium in the potassium permeability of human erythrocytes. Biochim Biophys Acta 30:653–654
Hoffman JF, Joiner W, Nehrke K et al (2003) The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells. Proc Natl Acad Sci U S A 100:7366–7371. https://doi.org/10.1073/pnas.1232342100
Maher AD, Kuchel PW (2003) The Gárdos channel: a review of the Ca2+-activated K+ channel in human erythrocytes. Int J Biochem Cell Biol 35:1182–1197
Grygorczyk R (1987) Temperature dependence of Ca2+-activated K+ currents in the membrane of human erythrocytes. Biochim Biophys Acta 902:159–168
Rapetti-Mauss R, Lacoste C, Picard V et al (2015) A mutation in the Gardos channel is associated with hereditary xerocytosis. Blood 126:1273–1280. https://doi.org/10.1182/blood-2015-04-642496
Glogowska E, Lezon-Geyda K, Maksimova Y et al (2015) Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis. Blood 126:1281–1284. https://doi.org/10.1182/blood-2015-07-657957
Fermo E, Bogdanova A, Petkova-Kirova P et al (2017) “Gardos Channelopathy”: a variant of hereditary stomatocytosis with complex molecular regulation. Sci Rep 7:1744. https://doi.org/10.1038/s41598-017-01591-w
Mankad VN (2001) Exciting new treatment approaches for pathyphysiologic mechanisms of sickle cell disease. Pediatr Pathol Mol Med 20:1–13
Ataga KI, Reid M, Ballas SK et al (2011) Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: a phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043). Br J Haematol 153:92–104. https://doi.org/10.1111/j.1365-2141.2010.08520.x
Bogdanova A, Makhro A, Kaestner L (2015) Calcium handling in red blood cells of sicke cell disease patients. In: Lewis ME (ed) Sickle cell disease: Genetics, Management and Prognosis, Nova Publishing, pp 29–59
Rapetti-Mauss R, Soriani O, Vinti H et al (2016) Senicapoc: a potent candidate for the treatment of a subset of Hereditary Xerocytosis caused by mutations in the Gardos channel. Haematologica 2016:149104. https://doi.org/10.3324/haematol.2016.149104
Christophersen P, Bennekou P (1991) Evidence for a voltage-gated, non-selective cation channel in the human red cell membrane. Biochim Biophys Acta 1065:103–106
Bennekou P (1993) The voltage-gated non-selective cation channel from human red cells is sensitive to acetylcholine. Biochim Biophys Acta 1147:165–167
Kaestner L, Christophersen P, Bernhardt I, Bennekou P (2000) The non-selective voltage-activated cation channel in the human red blood cell membrane: reconciliation between two conflicting reports and further characterisation. Bioelectrochemistry 52:117–125
Kaestner L (2011) Cation channels in erythrocytes – historical and future perspective. Open Biol J 4:27–34
Bouyer G, Thomas S, Egée S (2012) Patch-clamp analysis of membrane transport in erythrocytes. In: Patch clamp technique. InTech, Rijeka, pp 171–202
Bouyer G, Cueff A, Egée S et al (2011) Erythrocyte peripheral type benzodiazepine receptor/voltage-dependent anion channels are upregulated by Plasmodium falciparum. Blood 118:2305–2312. https://doi.org/10.1182/blood-2011-01-329300
Moroni M, Servin-Vences MR, Fleischer R et al (2018) Voltage gating of mechanosensitive PIEZO channels. Nat Commun 9:1096. https://doi.org/10.1038/s41467-018-03502-7
Kaestner L, Egee S (2018) Commentary: voltage gating of mechanosensitive PIEZO channels. Front Physiol 9:1565
Andersson T (2010) Exploring voltage-dependent ion channels in silico by hysteretic conductance. Math Biosci 226:16–27. https://doi.org/10.1016/j.mbs.2010.03.004
Zarychanski R, Schulz VP, Houston BL et al (2012) Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood 120:1908–1915. https://doi.org/10.1182/blood-2012-04-422253
Bae C, Gnanasambandam R, Nicolai C et al (2013) Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. Proc Natl Acad Sci U S A 110:E1162–E1168. https://doi.org/10.1073/pnas.1219777110
Kaestner L (2015) Channelizing the red blood cell: molecular biology competes with patch-clamp. Front Mol Biosci 2:46. https://doi.org/10.3389/fmolb.2015.00046
Syeda R, Xu J, Dubin AE et al (2015) Chemical activation of the mechanotransduction channel Piezo1. Elife. https://doi.org/10.7554/eLife.07369
Rotordam GM, Fermo E, Becker N et al (2019) A novel gain-of-function mutation of Piezo1 is functionally affirmed in red blood cells by high-throughput patch clamp. Haematologica 104(5). https://doi.org/10.3324/haematol.2018.201160
Lew VL, Tiffert T (2017) On the mechanism of human red blood cell longevity: roles of calcium, the sodium pump, PIEZO1, and Gardos channels. Front Physiol 8:977. https://doi.org/10.3389/fphys.2017.00977
Albuisson J, Murthy SE, Bandell M et al (2013) Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat Commun 4:1884. https://doi.org/10.1038/ncomms2899
Andolfo I, Alper SL, De Franceschi L et al (2013) Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. Blood 121:3925–3935. https://doi.org/10.1182/blood-2013-02-482489
Archer NM, Shmukler BE, Andolfo I et al (2014) Hereditary xerocytosis revisited. Am J Hematol 89:1142–1146. https://doi.org/10.1002/ajh.23799
Glogowska E, Schneider ER, Maksimova Y et al (2017) Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis. Blood 130:1845–1856. https://doi.org/10.1182/blood-2017-05-786004
Hertz L, Huisjes R, Llaudet-Planas E et al (2017) Is increased intracellular calcium in red blood cells a common component in the molecular mechanism causing anemia? Front Physiol 8:673. https://doi.org/10.3389/fphys.2017.00673
Steffen P, Jung A, Nguyen DB et al (2011) Stimulation of human red blood cells leads to Ca2+-mediated intercellular adhesion. Cell Calcium 50:54–61. https://doi.org/10.1016/j.ceca.2011.05.002
Kaestner L, Steffen P, Nguyen DB et al (2012) Lysophosphatidic acid induced red blood cell aggregation in vitro. Bioelectrochemistry 87:89–95. https://doi.org/10.1016/j.bioelechem.2011.08.004
Chung SM, Bae ON, Lim KM et al (2007) Lysophosphatidic acid induces thrombogenic activity through phosphatidylserine exposure and procoagulant microvesicle generation in human erythrocytes. Arterioscler Thromb Vasc Biol 27:414–421
Lew VL, Ortiz OE, Bookchin RM (1997) Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability. J Clin Invest 99:2727–2735. https://doi.org/10.1172/JCI119462
Browning JA, Robinson HC, Ellory JC, Gibson JS (2007) Deoxygenation-induced non-electrolyte pathway in red cells from sickle cell patients. Cell Physiol Biochem 19:165–174. https://doi.org/10.1159/000099204
Ma Y-L, Rees DC, Gibson JS, Ellory JC (2012) The conductance of red blood cells from sickle cell patients: ion selectivity and inhibitors. J Physiol Lond 590:2095–2105. https://doi.org/10.1113/jphysiol.2012.229609
Bae C, Sachs F, Gottlieb PA (2011) The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry 50:6295–6300. https://doi.org/10.1021/bi200770q
Hanggi P, Makhro A, Gassmann M et al (2014) Red blood cells of sickle cell disease patients exhibit abnormally high abundance of N-methyl D-aspartate receptors mediating excessive calcium uptake. Br J Haematol 167:252–264. https://doi.org/10.1111/bjh.13028
Makhro A, Wang J, Vogel J et al (2010) Functional NMDA receptors in rat erythrocytes. Am J Physiol Cell Physiol 298:C1315–C1325. https://doi.org/10.1152/ajpcell.00407.2009
Bogdanova A, Makhro A, Goede J et al (2009) NMDA receptors in mammalien erythrocytes. Clin Biochem 42:1858–1859
Makhro A, Kaestner L, Bogdanova A (2017) NMDA receptor activity in circulating red blood cells: methods of detection. Methods Mol Biol 1677:265–282, 484. https://doi.org/10.1007/978-1-4939-7321-7_15
Hanggi P, Telezhkin V, Kemp PJ et al (2015) Functional plasticity of the N-methyl-d-aspartate receptor in differentiating human erythroid precursor cells. Am J Physiol Cell Physiol 308:C993–C1007. https://doi.org/10.1152/ajpcell.00395.2014
Hegemann I, Sasselli C, Valeri F, Makhro A, Müller R, Bogdanova A, Manz MG, Gassmann M, Goede JS. Memantine treatment is well tolerated by sickle cell patients and improves erythrocyte stability: phase II study MemSID (submitted)
Bogdanova A, Makhro A, Hegemann I, Seiler E, Bogdanov N, Simionato G, Kaestner L, Claveria V, Saselli C, Torgeson P, Manz M, Goede J, Gassmann M. Improved maturation and increased stability of red blood cells of sickle cell patients on memantine treatment (submitted)
Makhro A, Haider T, Wang J et al (2016) Comparing the impact of an acute exercise bout on plasma amino acid composition, intraerythrocytic Ca2+ handling, and red cell function in athletes and untrained subjects. Cell Calcium 60:235–244. https://doi.org/10.1016/j.ceca.2016.05.005
Thomas SLY, Bouyer G, Cueff A et al (2011) Ion channels in human red blood cell membrane: actors or relics? Blood Cells Mol Dis 46:261–265. https://doi.org/10.1016/j.bcmd.2011.02.007
Schein SJ, Colombini M, Finkelstein A (1976) Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel obtained from paramecium mitochondria. J Membr Biol 30:99–120
Thinnes FP, Flörke H, Winkelbach H et al (1994) Channel active mammalian porin, purified from crude membrane fractions of human B lymphocytes or bovine skeletal muscle, reversibly binds the stilbene-disulfonate group of the chloride channel blocker DIDS. Biol Chem Hoppe Seyler 375:315–322
Marginedas-Freixa I, Hattab C, Bouyer G et al (2016) TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood. Sci Rep 6:33516. https://doi.org/10.1038/srep33516
McEnery MW, Snowman AM, Trifiletti RR, Snyder SH (1992) Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. Proc Natl Acad Sci U S A 89:3170–3174
Le Fur G, Vaucher N, Perrier ML et al (1983) Differentiation between two ligands for peripheral benzodiazepine binding sites, [3H]RO5-4864 and [3H]PK 11195, by thermodynamic studies. Life Sci 33:449–457
Olson JM, Ciliax BJ, Mancini WR, Young AB (1988) Presence of peripheral-type benzodiazepine binding sites on human erythrocyte membranes. Eur J Pharmacol 152:47–53
Canat X, Carayon P, Bouaboula M et al (1993) Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells. Life Sci 52:107–118
Shoshan-Barmatz V, De Pinto V, Zweckstetter M et al (2010) VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol Asp Med 31:227–285. https://doi.org/10.1016/j.mam.2010.03.002
Moran O, Sorgato MC (1992) High-conductance pathways in mitochondrial membranes. J Bioenerg Biomembr 24:91–98
Benz R (1994) Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins. Biochim Biophys Acta 1197:167–196
Hodge T, Colombini M (1997) Regulation of metabolite flux through voltage-gating of VDAC channels. J Membr Biol 157:271–279
Gincel D, Silberberg SD, Shoshan-Barmatz V (2000) Modulation of the voltage-dependent anion channel (VDAC) by glutamate. J Bioenerg Biomembr 32:571–583
Báthori G, Csordás G, Garcia-Perez C et al (2006) Ca2+-dependent control of the permeability properties of the mitochondrial outer membrane and voltage-dependent anion-selective channel (VDAC). J Biol Chem 281:17347–17358. https://doi.org/10.1074/jbc.M600906200
Tong Q, Hirschler-Laszkiewicz I, Zhang W et al (2008) TRPC3 is the erythropoietin-regulated calcium channel in human erythroid cells. J Biol Chem 283:10385–10395. https://doi.org/10.1074/jbc.M710231200
Hirschler-Laszkiewicz I, Tong Q, Conrad K et al (2009) TRPC3 activation by erythropoietin is modulated by TRPC6. J Biol Chem 284:4567–4581. https://doi.org/10.1074/jbc.M804734200
Kucherenko YV, Bhavsar SK, Grischenko VI et al (2010) Increased cation conductance in human erythrocytes artificially aged by glycation. J Membr Biol 235:177–189. https://doi.org/10.1007/s00232-010-9265-2
Danielczok J, Hertz L, Ruppenthal S et al (2017) Does erythropoietin regulate TRPC channels in red blood cells? Cell Physiol Biochem 41:1219–1228. https://doi.org/10.1159/000464384
Foller M, Kasinathan RS, Koka S et al (2008) TRPC6 contributes to the Ca2+ leak of human erythrocytes. Cell Physiol Biochem 21:183–192
Dietrich A, Gudermann T (2014) TRPC6: physiological function and pathophysiological relevance. Handb Exp Pharmacol 222:157–188. https://doi.org/10.1007/978-3-642-54215-2_7
Pinet C, Antoine S, Filoteo AG et al (2002) Reincorporated plasma membrane Ca2+-ATPase can mediate B-type Ca2+ channels observed in native membrane of human red blood cells. J Membr Biol 187:185–201. https://doi.org/10.1007/s00232-001-0163-5
Romero PJ, Romero EA, Mateu D et al (2006) Voltage-dependent calcium channels in young and old human red cells. Cell Biochem Biophys 46:265–276. https://doi.org/10.1385/CBB:46:3:265
Andrews DA, Yang L, Low PS (2002) Phorbol ester stimulates a protein kinase C-mediated agatoxin-TK-sensitive calcium permeability pathway in human red blood cells. Blood 100:3392–3399
Wagner-Britz L, Wang J, Kaestner L, Bernhardt I (2013) Protein kinase Cα and P-type Ca channel CaV2.1 in red blood cell calcium signalling. Cell Physiol Biochem 31:883–891. https://doi.org/10.1159/000350106
Kaestner L, Wang X, Hertz L, Bernhardt I (2018) Voltage-activated ion channels in non-excitable cells – a viewpoint regarding their physiological justification. Front Physiol 9:450
Tiffert T, Bookchin RM, Lew VL (2003) Calcium homeostasis in normal and abnormal human red cells. In: Bernhardt I, Ellory C (eds) Red cell membrane transport in health and disease. Springer, Berlin, pp 373–405
Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3:a003947. https://doi.org/10.1101/cshperspect.a003947
Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16:521–555. https://doi.org/10.1146/annurev.cellbio.16.1.521
Petkova-Kirova P, Hertz L, Makhro A et al (2018) A previously unrecognized Ca2+-inhibited non-selective cation channel in red blood cells. HemaSphere, 2:e146
Flatt JF, Bawazir WM, Bruce LJ (2014) The involvement of cation leaks in the storage lesion of red blood cells. Front Physiol 5:214. https://doi.org/10.3389/fphys.2014.00214
Lipp P, Kaestner L (2014) Detecting calcium in cardiac muscle: fluorescence to dye for. Am J Physiol Heart Circ Physiol 307:H1687–H1690. https://doi.org/10.1152/ajpheart.00468.2014
Kaestner L, Tabellion W, Weiss E et al (2006) Calcium imaging of individual erythrocytes: problems and approaches. Cell Calcium 39:13–19. https://doi.org/10.1016/j.ceca.2005.09.004
Jarrett HW, Kyte J (1979) Human erythrocyte calmodulin. Further chemical characterization and the site of its interaction with the membrane. J Biol Chem 254:8237–8244
Leinders T, van Kleef RG, Vijverberg HP (1992) Single Ca2+-activated K+ channels in human erythrocytes: Ca2+ dependence of opening frequency but not of open lifetimes. Biochim Biophys Acta 1112:67–74
Stout JG, Zhou Q, Wiedmer T, Sims PJ (1998) Change in conformation of plasma membrane phospholipid scramblase induced by occupancy of its Ca2+ binding site. Biochemistry 37:14860–14866. https://doi.org/10.1021/bi9812930
Woon LA, Holland JW, Kable EP, Roufogalis BD (1999) Ca2+ sensitivity of phospholipid scrambling in human red cell ghosts. Cell Calcium 25:313–320
Bitbol M, Fellmann P, Zachowski A, Devaux PF (1987) Ion regulation of phosphatidylserine and phosphatidylethanolamine outside-inside translocation in human erythrocytes. Biochim Biophys Acta 904:268–282
Murakami T, Hatanaka M, Murachi T (1981) The cytosol of human erythrocytes contains a highly Ca2+-sensitive thiol protease (calpain I) and its specific inhibitor protein (calpastatin). J Biochem 90:1809–1816
Salamino F, De Tullio R, Mengotti P et al (1993) Site-directed activation of calpain is promoted by a membrane-associated natural activator protein. Biochem J 290(Pt 1):191–197
Bergamini CM, Signorini M (1993) Studies on tissue transglutaminases: interaction of erythrocyte type-2 transglutaminase with GTP. Biochem J 291(Pt 1):37–39
Almaraz L, García-Sancho J, Lew VL (1988) Calcium-induced conversion of adenine nucleotides to inosine monophosphate in human red cells. J Physiol Lond 407:557–567
Kohout SC, Corbalán-García S, Torrecillas A et al (2002) C2 domains of protein kinase C isoforms alpha, beta, and gamma: activation parameters and calcium stoichiometries of the membrane-bound state. Biochemistry 41:11411–11424. https://doi.org/10.1021/bi026401k
Schwarz W, Grygorczyk R, Hof D (1989) Recording single-channel currents from human red cells. Methods Enzymol 173:112–121
Grygorczyk R, Schwarz W, Passow H (1984) Ca2+-activated K+ channels in human red cells. Comparison of single-channel currents with ion fluxes. Biophys J 45:693–698. https://doi.org/10.1016/S0006-3495(84)84211-3
Grygorczyk R, Schwarz W (1985) Ca2+-activated K+ permeability in human erythrocytes: modulation of single-channel events. Eur Biophys J 12:57–65
Leinders T, van Kleef RG, Vijverberg HP (1992) Distinct metal ion binding sites on Ca2+-activated K+ channels in inside-out patches of human erythrocytes. Biochim Biophys Acta 1112:75–82
Dunn PM (1998) The action of blocking agents applied to the inner face of Ca2+-activated K+ channels from human erythrocytes. J Membr Biol 165:133–143
Wolff D, Cecchi X, Spalvins A, Canessa M (1988) Charybdotoxin blocks with high affinity the Ca-activated K+ channel of Hb A and Hb S red cells: individual differences in the number of channels. J Membr Biol 106:243–252
Qadri SM, Kucherenko Y, Lang F (2011) Beauvericin induced erythrocyte cell membrane scrambling. Toxicology 283:24–31. https://doi.org/10.1016/j.tox.2011.01.023
Kucherenko Y, Zelenak C, Eberhard M et al (2012) Effect of casein kinase 1α activator pyrvinium pamoate on erythrocyte ion channels. Cell Physiol Biochem 30:407–417. https://doi.org/10.1159/000339034
Kucherenko YV, Wagner-Britz L, Bernhardt I, Lang F (2013) Effect of chloride channel inhibitors on cytosolic Ca2+ levels and Ca2+-activated K+ (Gardos) channel activity in human red blood cells. J Membr Biol 246:315–326. https://doi.org/10.1007/s00232-013-9532-0
Baunbaek M, Bennekou P (2008) Evidence for a random entry of Ca2+ into human red cells. Bioelectrochemistry 73:145–150. https://doi.org/10.1016/j.bioelechem.2008.04.006
Seear RV, Lew VL (2011) IKCa agonist (NS309)-elicited all-or-none dehydration response of human red blood cells is cell-age dependent. Cell Calcium 50:444–448. https://doi.org/10.1016/j.ceca.2011.07.005
Schatzmann HJ (1973) Dependence on calcium concentration and stoichiometry of the calcium pump in human red cells. J Physiol Lond 235:551–569
Lines GT, Sande JB, Louch WE et al (2006) Contribution of the Na+/Ca2+ exchanger to rapid Ca2+ release in cardiomyocytes. Biophys J 91:779–792. https://doi.org/10.1529/biophysj.105.072447
Chu H, Puchulu-Campanella E, Galan JA et al (2012) Identification of cytoskeletal elements enclosing the ATP pools that fuel human red blood cell membrane cation pumps. Proc Natl Acad Sci U S A 109:12794–12799. https://doi.org/10.1073/pnas.1209014109
Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415:198–205. https://doi.org/10.1038/415198a
Rasband MN, Shrager P (2000) Ion channel sequestration in central nervous system axons. J Physiol Lond 525(Pt 1):63–73. https://doi.org/10.1111/j.1469-7793.2000.00063.x
Dyrda A, Cytlak U, Ciuraszkiewicz A et al (2010) Local membrane deformations activate Ca2+-dependent K+ and anionic currents in intact human red blood cells. PLoS One 5:e9447. https://doi.org/10.1371/journal.pone.0009447
Liappis N (1972) Sodium-, potassium- and chloride-concentrations in the serum of infants, children and adults. Monatsschr Kinderheilkd 120:138–142
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Kaestner, L., Bogdanova, A., Egee, S. (2020). Calcium Channels and Calcium-Regulated Channels in Human Red Blood Cells. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 1131. Springer, Cham. https://doi.org/10.1007/978-3-030-12457-1_25
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DOI: https://doi.org/10.1007/978-3-030-12457-1_25
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