Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons
Ethanol increased the frequency of miniature glycinergic currents [miniature inhibitory postsynaptic currents (mIPSCs)] in cultured spinal neurons. This effect was dependent on intracellular calcium augmentation, since preincubation with BAPTA (an intracellular calcium chelator) or thapsigargin [a sarco(endo) plasmic reticulum Ca2+ -AT-Pase (SERCA) pump inhibitor] significantly attenuated this effect. Similarly, U73122 (a phospholipase C inhibitor) or 2-aminoethoxydiphenyl borate [2-APB, an inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) inhibitor] reduced this effect. Block of ethanol action was also achieved after preincubation with Rp-cAMPS, inhibitor of the adenylate cyclase (AC)/PKA signaling pathway. These data suggest that there is a convergence at the level of IP3R that accounts for presynaptic ethanol effects. At the postsynaptic level, ethanol increased the decay time constant of mIPSCs in a group of neurons (30 +/- 10% above control, n = 13/26 cells). On the other hand, the currents activated by exogenously applied glycine were consistently potentiated (55 +/- 10% above control, n = 11/12 cells), which suggests that ethanol modulates synaptic and nonsynaptic glycine receptors (GlyRs) in a different fashion. Supporting the role of G protein modulation on ethanol responses, we found that a nonhydrolyzable GTP analog [guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)] increased the decay time constant in similar to 50% of the neurons (28 +/- 12%, n = 11/19 cells) but potentiated the glycine-activated Cl- current in most of the neurons examined (83 +/- 29%, n = 7/9 cells). In addition, confocal microscopy showed that alpha 1-containing GlyRs colocalized with G beta and Piccolo (a presynaptic cytomatrix protein) in similar to 40% of synaptic receptor clusters, suggesting that colocalization of G beta gamma and GlyRs might account for the difference in ethanol sensitivity at the postsynaptic level.
|Título según WOS:||Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons|
|Título según SCOPUS:||Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons|
|Título de la Revista:||JOURNAL OF NEUROPHYSIOLOGY|
|Editorial:||AMER PHYSIOLOGICAL SOC|
|Fecha de publicación:||2014|
|Página de inicio:||1940|