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

Abstract

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.

Ca2+/calmodulin‐dependent protein kinase II and Dimethyl Sulfoxide affect the sealing frequencies of transected hippocampal neurons

“…At higher concentrations, ~10 mol % (4.3 M or 30.6% v/v), DMSO promotes the formation of water-filled membrane pores (de Ménorval et al 2012). DMSO has also been shown to disrupt many proteins such as cation channels (0.1 – 2 M or 0.71 – 14.2% v/v, Nardid et al 2013), cytoskeletal proteins (1.4 M or 10% v/v, Sanger et al 1980), and albumins (2.82 M or 20% v/v, Batista et al 2014). At yet-higher concentrations (5 M or 35% v/v), DMSO can act as a cell-cell fusogen (Ahkong et al 1975).…”

The TRPM4 channel inhibitor 9‐phenanthrol

“…Nevertheless, in general, this use of DMSO should be avoided because a high concentration of DMSO may introduce new side effects. DMSO inhibits non‐selective cation channels such as NMDA and AMPA glutamate receptors when used at or above 0.5% (Lu and Mattson, ), and it inhibits whole‐cell non‐selective cationic currents in erythrocytes at or above 1% (Nardid et al ., ).…”

On the involvement of cell volume regulation mechanisms in post-hypertonic lysis and slow-freezing injury of human erythrocytes and its broader cryobiological significance

“…27,44,45 Specifically to human RBCs, experimental studies also support the involvement of ion transport pathways in the osmotic response of RBCs as the ion flux rates may be high enough to result in considerable KCl loss within ~15 minutes 67 (action equivalent to RVD response) or increase of intracellular Na in 30 minutes (RVI). 50 Furthermore, wholecell recordings of 68 to 500 pico-siemens cation conductances were reported, 51,68,69 corresponding to about a 3 to 4 order increase compared to the normal isotonic value. 70 This experimental observation supports the relatively high rate of predicted NaCl loading occurring only via physiological ion transport pathways (consult Figure 6).…”

“…Indeed, there is evidence that dimethyl sulfoxide inhibits the non-selective cation channels of human erythrocytes. 68 Inhibition of these ion channels would decrease the extent of cation leaks and thus reduce the post-hypertonic lysis. The mechanism of the inhibitory effect of dimethyl sulfoxide on the non-selective cation channels has yet to be elucidated.…”

“…However, while dimethyl sulfoxide was found to inhibit the cation fluxes, glycerol did not affect them. 68 Since both additives offer cryoprotection to RBCs, these results suggest that the protective action of these agents might also be facilitated by their non-specific effect on the stimuli triggering the ion channels. The non-selective cation channels of human RBCs were shown to be sensitive to cell volume and internal and external Clconcentration.…”