Cyanide interaction with redox modulatory sites enhances NMDA receptor responses

Non‐specificity of ethylene inhibitors: ‘double‐edged’ tools to find out new targets involved in the root morphogenetic programme

“…; Sun et al . ). In addition, cyanide degradation by β‐cyanoalanine synthetase produces hydrogen sulphide (H 2 S), another gaseous compound that enhances NMDA receptor‐mediated responses and facilitates the induction of their long‐term potentiation in mammals (Kimura ).…”

“…Although GLRs have a similar ATD domain, no study has yet been conducted in plants to highlight positive or negative allosteric modulators. Intriguingly, it has been shown that cyanide concentrations as low as 10 lM can act as a potent neuromodulator of iGluRs of the central nervous system and enhances accumulation of Ca 2+ in rat cerebellar granule cells (Borowitz et al 1997;Sun et al 1999). In addition, cyanide degradation by b-cyanoalanine synthetase produces hydrogen sulphide (H 2 S), another gaseous compound that enhances NMDA receptor-mediated responses and facilitates the induction of their long-term potentiation in mammals (Kimura 2013).…”

The two faces of cyanide: an environmental toxin and a potential novel mammalian gasotransmitter

“…For example, cyanide (at the relatively low concentration of 50–100 µ m ) was shown to enhance NMDA receptor activation and the consequent calcium mobilization response [ 64 , 65 ]. Cyanide, at millimolar concentrations, was reported to exert selective effects on NMDA receptor subtypes: It potentiates the activation of NR1/NR2A receptors, most likely via the chemical reduction of NR2A, but it does not potentiate the activation NR1/NR2B receptors (rather, it exerts a slight inhibitory effect) [ 66 , 67 ]. Exposure of various cell types to cyanide was also found to produce an intracellular Ca 2+ response, which, at low cyanide concentrations (starting at 1 µ m ) produces a stimulation of intracellular inositol triphosphate level, followed by Ca 2+ mobilization from intracellular calcium pools [ 64 ].…”

“…Moreover, as noted above, cyanide already at relatively low concentrations (e.g., 50 µ m ) enhances NMDA receptor activation. This response has been demonstrated in reductionist preparations that don’t contain mitochondria (e.g., measurement of single channel activity in excised outside‐out membrane patches) and therefore must be the consequence of direct effects of cyanide on these receptors, possibly via a direct action on redox sensitive disulfide groups [ 66 , 67 ]. At higher concentrations [1 m m ], cyanide may also, at least in part, act in a direct fashion on the NMDA receptor, by interacting with its Mg 2+ block [ 98 ].…”

Is there evidence that cyanide can act as a neuromodulator?

“…Although cyanide binding to tissue constituents may result in underestimation of locally produced cyanide, this is a biologically active concentration. In fact, cyanide concentration as low as 10 mM significantly enhances N-methyl-D-aspartate (NMDA) induced accumulation of cytosolic free Ca 2þ in rat cerebellar granule cells (5,12).…”