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The Journal of Neurophysiology Vol. 84 No. 5 November 2000, pp. 2409-2416
Copyright ©2000 by the American Physiological Society
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195-7290
Eggers, Erika D.,
Jennifer A. O'Brien, and
Albert J. Berger.
Developmental Changes in the Modulation of Synaptic Glycine
Receptors by Ethanol. J. Neurophysiol. 84: 2409-2416, 2000. During postnatal motoneuron development, the
glycine receptor (GlyR) 
subunit changes from 2 (fetal) to 1
(adult). To study the effect this change has on ethanol potentiation of
GlyR currents in hypoglossal motoneurons (HMs), we placed neurons into
two groups: neonate [postnatal day 1 to 3 (P1-3)], primarily expressing 2, and juvenile
(P9-13), primarily expressing 1. We found that
glycinergic spontaneous miniature inhibitory postsynaptic currents
(mIPSCs) in neonate HMs are less sensitive to ethanol than in
juveniles. Thirty millimolar ethanol increased the amplitude of
juvenile mIPSCs but did not significantly change neonatal mIPSCs.
However, 100 mM ethanol increased the amplitudes of both neonate and
juvenile mIPSCs. There was a significant difference between age groups in the average ethanol-induced increase in mIPSC amplitude for 10, 30, 50, and 100 mM ethanol. In both age groups ethanol increased the
frequency of glycinergic mIPSCs, but there was no difference in the
amount of frequency increase between age groups. Ethanol (100 mM) also
potentiated evoked IPSCs (eIPSCs) in both neonate and juvenile HMs. As
we observed for mIPSCs, 30 mM ethanol increased the amplitude of
juvenile eIPSCs, but had no significant effect on eIPSCs in neonate
HMs. Ethanol also potentiated currents induced by exogenously applied
glycine in both neonate and juvenile HMs. These results suggest that
ethanol directly modulates the GlyR. To investigate possible mechanisms
for this, we analyzed the time course of mIPSCs and single-channel
conductance of the GlyR in the presence and absence of ethanol. We
found that ethanol did not significantly change the time course of
mIPSCs. We also determined that ethanol did not significantly change
the single-channel conductance of synaptic GlyRs, as estimated by
nonstationary noise analysis of mIPSCs. We conclude that the adult form
of the native GlyR is more sensitive to ethanol than the fetal form.
Further, enhancement of GlyR currents involves mechanisms other than an
increase in the single-channel conductance or factors that alter the
decay kinetics.
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