Cyanide interaction with redox modulatory sites enhances NMDA receptor responses

Cyanide overproduction impairs cellular bioenergetics in Down syndrome

“…Low levels of cyanide were found to be produced in the brain and in neuronal cell lines in several reports published in the early 2000's [ 5 , 6 ]. It was also suggested that endogenous cyanide generation in neurons may involve a peroxidase mechanism [ 5 , 6 , [16] , [17] , [18] , [19] ]. Recent work has provided new insights into cyanide biogenesis and its physiological role.…”

“…However, additional actions may also contribute to cyanide's adverse cellular effects; cyanide is known to induce intracellular calcium overload via calcium-channel opening and mobilization of calcium from intracellular pools. Cyanide can activate NMDA receptors [ 19 ], which may also contribute to its neurotoxic effects via inducing or potentiating excitotoxic neuronal damage. In addition, Complex IV inhibition – in part via the ATP depletion it causes – can trigger further downstream damage.…”

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 ).…”

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 ].…”