TRPC6 Contributes to the Ca&lt;sup&gt;2+&lt;/sup&gt; Leak of Human Erythrocytes

Föller, Michael; Kasinathan, Ravi S.; Koka, Saisudha; Lang, Camelia; Shumilina, Ekaterina; Birnbaumer, Lutz; Läng, Florian; Huber, Stephan M.

doi:10.1159/000113760

Cited by 152 publications

(137 citation statements)

References 59 publications

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“…The voltageindependent cation channels were shown to be partially related to TRPC3/6/7 channels (Foller et al 2008). Recent data demonstrated the existence of NMDA receptors in rat (Makhro et al 2010) and AMPA receptors in human (Föller et al 2009) erythrocytes.…”

Section: Discussionmentioning

confidence: 98%

Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes

Nardid¹,

Schetinskey²,

Kucherenko³

2013

gpb

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Abstract. Dimethyl sulfoxide (DMSO), a by-product of the pulping industry, is widely used in biological research, cryobiology and medicine. On cellular level DMSO was shown to suppress NMDA-AMPA channels activation, blocks Na + channel activation and attenuates Ca 2+ influx (Lu and Mattson 2001). In the present study we explored the whole-cell patch-clamp to examine the acute effect of high concentrations of DMSO (0.1-2 mol/l) on cation channels activity in human erythrocytes. Acute application of DMSO (0.1-2 mol/l) dissolved in Cl --containing saline buffer solution significantly inhibited cation conductance in human erythrocytes. Inhibition was concentration-dependent and had an exponential decay profile. DMSO (2 mol/l) induced cation inhibition in Cl --containing saline solutions of: 40.3 ± 3.9% for K + , 35.4 ± 3.1% for Ca 2+ and 47.4 ± 1.9% for NMDG + . Substitution of Cl -with gluconate -increased the inhibitory effect of DMSO on the Na + current. Inhibitory effect of DMSO was neither due to high permeability of erythrocytes to DMSO nor to an increased tonicity of the bath media since no effect was observed in 2 mol/l glycerol solution. In conclusion, we have shown that high concentrations of DMSO inhibit the non-selective cation channels in human erythrocytes and thus protect the cells against Na + and Ca 2+ overload. Possible mechanisms of DMSO effect on cation conductance are discussed.

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Section: Discussionmentioning

confidence: 98%

Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes

Nardid¹,

Schetinskey²,

Kucherenko³

2013

gpb

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“…During aging, this calcium homeostasis is disrupted and there is a gradual increase in intracellular calcium (44,93). Increased intra-cellular calcium activates the Gordo's potassium channel causing the leakage of potassium from the cell, resulting in cell shrinkage and impaired deformability (15,32). Calcium also activates u-calpain, transglutaminase-2, and some caspases that can degrade/cross-link cytoskeleton proteins (79).…”

Section: The Removal Of Rbcs From the Circulationmentioning

confidence: 99%

Hemoglobin Redox Reactions and Red Blood Cell Aging

Rifkind

Nagababu

2013

Antioxidants & Redox Signaling

134

112

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Significance: The physiological mechanism(s) for recognition and removal of red blood cells (RBCs) from circulation after 120 days of its lifespan is not fully understood. Many of the processes thought to be associated with the removal of RBCs involve oxidative stress. We have focused on hemoglobin (Hb) redox reactions, which is the major source of RBC oxidative stress. Recent Advances: The importance of Hb redox reactions have been shown to originate in large parts from the continuous slow autoxidation of Hb producing superoxide and its dramatic increase under hypoxic conditions. In addition, oxidative stress has been shown to be associated with redox reactions that originate from Hb reactions with nitrite and nitric oxide (NO) and the resultant formation of highly toxic peroxynitrite when NO reacts with superoxide released during Hb autoxidation. Critical Issues: The interaction of Hb, particularly under hypoxic conditions with band 3 of the RBC membrane is critical for the generating the RBC membrane changes that trigger the removal of cells from circulation. These changes include exposure of antigenic sites, increased calcium leakage into the RBC, and the resultant leakage of potassium out of the RBC causing cell shrinkage and impaired deformability. Future Directions: The need to understand the oxidative damage to specific membrane proteins that result from redox reactions occurring when Hb is bound to the membrane. Proteomic studies that can pinpoint the specific proteins damaged under different conditions will help elucidate the cellular aging processes that result in cells being removed from circulation. Antioxid. Redox Signal. 18, 2274-2283.

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“…Decreased ATP-dependent transport may be very well one of the consequences of phosphatidylserine exposure (Soupene & Kuypers, 2006). Besides, energy depletion involves activation of PKC and PKC-dependent phosphorylation of membrane proteins with subsequent stimulation of eryptosis (Föller et al, 2008). …”

Section: Energy Depletionmentioning

confidence: 99%