Caesium ions: a glycine‐activated channel agonist in rat spinal cord neurones grown in cell culture

Abstract

-upon-Tyne NE4 6BE1 The chloride (Cl-) currents activated by caesium ions (Cs'), glycine and y-aminobutyric acid (GABA) were compared following their application to rat neurones that had been grown in cell culture. Recordings were made using the whole-cell patch clamp technique under voltage clamp conditions. 2 In spinal cord neurones, bicuculline methiodide antagonized GABA-activated currents more effectively than Cs+-or glycine-activated currents. However, strychnine was more effective at blocking the currents activated by Cs' or glycine than those activated by GABA.3 Of the 3 agonists, only GABA activated currents in cells from the intermediate lobe of the rat pituitary. 4 In spinal neurones the size of the currents activated by 70mm Cs+ was correlated to the size of the currents activated by 15 yM glycine (P < 0.005; n = 10, Spearman's rank correlation), but there was no significant correlation between the size of the currents activated by these agents and 10JM GABA. 5 The joint application of glycine and Cs + activated currents that were approximately twice as big as the sums of the currents activated by separate applications of the same doses. This synergism was consistent with Cs+ acting at the same receptor as glycine (7 pM glycine being equivalent to 31 + 7mM Cs+). 6 It was concluded that Cs+ activates the same Cl-channel as the inhibitory neurotransmitter glycine.

Cesium activates the neurotransmitter receptor for glycine

“…Altogether, the findings of this and earlier studies ( Lewis et al, 1989 ; Smith and McBurney, 1989 ) reveal that Cs + is an agonist of GlyRs, which can help to provide scientific support for the FDA alert and may contribute to a better understanding of the adverse health effects associated with the intake of Cs + , although these seem to result primarily from cardiovascular dysfunction.…”

“…Additionally, monovalent cations, such as potassium, rubidium and cesium exhibit distinct voltage-dependent gating behavior in various members of the two-pore domain potassium channels ( Schewe et al, 2016 ). Most importantly, cesium was found to activate the same chloride channel as glycine, which sparked discussions about their association already three decades ago ( Lewis et al, 1989 ; Smith and McBurney, 1989 ). Cesium chloride is advertised as an alternative therapy agent for different types of cancer, but prolonged self-administration leads to severe health decline involving neuronal and cardiovascular dysfunction ( Dalal et al, 2004 ; Sessions et al, 2013 ).…”

Inorganic, monovalent cations compete with agonists for the transmitter binding site of nicotinic acetylcholine receptors

“…Finally, we note that most, if not all, neurotransmitters have an amino moiety that is cationic at physiological pH. It is thus possible that a similar, or more aggressive, competition between transmitter and ion takes place at other receptors (Smith and McBurney, 1989;Hirano et al, 1987). At some synapses changes in the ionic composition of the synaptic gap (for example, an increase in extracellular [K+]) may modulate the amplitude and kinetics of the synaptic response.…”

Molecular Structure and Function of the Glycine Receptor Chloride Channel

“…Because ivermectin-gated currents have a different pharmacology to glycine-gated currents, and glycine binding site mutations do not drastically affect its sensitivity (342), ivermectin appears to activate the GlyR via a novel mechanism. Apart from cesium (352), ivermectin is the only non-amino acid agonist of the GlyR to be identified to date.…”