Taurine activates glycine and GABAA receptor currents in anoxia-tolerant painted turtle pyramidal neurons

Abstract

Unlike anoxia-intolerant mammals, painted turtles can survive extended periods without oxygen. This is partly accomplished by an anoxia-mediated increase in gamma-aminobutyric acid (GABA) release, which activates GABA receptors and mediates spike arrest in turtle neurons via shunting inhibition. Extracellular taurine levels also increase during anoxia; why this occurs is unknown but it is speculated that glycine and/or GABA receptors are involved. Given the general importance of inhibitory neurotransmission in the anoxia-tolerant painted turtle brain, we investigated the function of taurine as an inhibitory neuromodulator in turtle pyramidal neurons. Using whole-cell patch-clamp electrophysiological methods to record from neurons within a cortical brain sheet, we found that taurine depolarized membrane potential by ∼8 mV, increased whole-cell conductance ∼2-fold, and induced an inward current that possessed characteristics similar to GABA- and glycine-evoked currents. These effects were mitigated following glycine receptor antagonism with strychnine and GABA receptor antagonism with gabazine, bicuculine or picrotoxin, but were unchanged following GABA or glutamatergic receptor inhibition. These data indicate that a high concentration of taurine mediates its effects through both glycine and GABA receptors, and suggests that taurine, in addition to GABA, inhibits neuronal activity during anoxia in the turtle cortex.

Taurine Promotes Neurite Outgrowth and Synapse Development of Both Vertebrate and Invertebrate Central Neurons

“…For example, taurine has been reported to induce dose-dependent effects on immature hippocampal neurons in both excitatory and inhibitory directions (Chen et al, 2014 ; Winkler et al, 2019 ); it enhances neuronal excitability in the immature neocortex (Sava et al, 2014 ), while it exhibits a dominant, inhibitory effect on neuronal activity in the mature CNS (Kilb and Fukuda, 2017 ). Also, taurine at mM concentrations inhibits neuronal activity during anoxia in turtle central neurons via both glycine and GABA A receptors (Miles et al, 2018 ). Consistently, our data indicate that taurine at mM concentrations could also negatively regulate neuronal firing activity in Lymnaea neurons ( Figure 5C ) in a cell-specific manner.…”

“…Like vertebrates, taurine is present in the nervous system of many invertebrates (Allen and Garrett, 1971;McCaman and Stetzler, 1977). Specifically, in marine invertebrates, taurine's robust role in osmoregulation is well characterized (Lange, 1963;Allen and Garrett, 1971;Gilles, 1972;Smith and Pierce, 1987;Miles et al, 2018). Other potential roles of taurine in invertebrates have been suggested such as an H 2 S scavenger in hydrothermal vent invertebrates (Koito et al, 2018), a source of energy for marine prokaryotes (Clifford et al, 2019), and a regulator of temperature tolerance in the fish Preccottus glehnii (Karanova, 2009).…”

Cytoskeletal Arrest: An Anoxia Tolerance Mechanism

“…In the basal forebrain of hibernating Syrian hamsters, cholinergic neurons express phosphorylated tau, while tau phosphorylation is largely absent in γ-amino butyric acid (GABA)ergic neurons [ 112 ]. In painted turtles [ 44 , 71 ] and goldfish [ 113 ], GABAergic inhibition of pyramidal cells by less abundant stellate cells [ 114 , 115 ] is a key mechanism of anoxia tolerance. If selective phosphorylation of tau occurs in anoxic turtles and fish, as it does in hamsters, then excitatory synapses could be inhibited while relatively less abundant inhibitory synapses are maintained.…”

“…This reduction contributes to neuronal anoxia tolerance, as indicated by cell viability [ 191 ]. ROS scavenging of painted turtle neurons mimics anoxic signalling by facilitating inhibitory GABAergic signalling [ 44 , 192 ]. Similarly, ROS production decreases by 10% with the onset of anoxia in goldfish brain, and ROS scavenging mimics anoxic inhibition of excitatory actional potential firing [ 193 ].…”

“… Organization of F-actin and microtubules in a cultured western painted turtle hepatocyte. Turtle hepatocytes were isolated as part of another study which was approved by the University of Toronto Animal Care Committee, and turtles were supplied by Niles Biological (Sacramento, CA, USA) and housed as described previously [ 44 ]. Hepatocytes were isolated as described by [ 11 ] and with sterile conditions, but with the addition of 1X Gibco MEM amino acids, 1X Gibco NEM amino acids, 1X Gibco MEM vitamin solution, 1X Pen-strep (Sigma Aldrich, St. Louis, MO, USA), and 200 μg/mL gentamicin sulphate (Bioshop) to the final media.…”