Glycine receptors, mediating inhibition in spinal cord and brainstem, are modulated by intracellular Ca²⁺, whose increase leads to the fast potentiation of glycine-activated currents (Fucile et al. 2000). To understand the physiological relevance of this Ca²⁺-dependent modulation, we analysed the effects of intracellular Ca²⁺ increase on glycinergic synaptic currents. Patch-clamp recordings were performed from visually identified motoneurons of the hypoglossal nucleus in rat (P6-P9) brainstem acute slices (250 µm). The rats were humanely killed and all procedures complied with the guidelines of the French Animal Care Committee. In the presence of glutamatergic (CNQX, 10 µM, AP5, 40 µM) and GABAergic (bicuculline, 20 µM) blockers, stable strychnine-sensitive glycinergic synaptic currents were evoked by stimulation with an extracellular electrode close to the recorded neuron. To increase the cytosolic Ca²⁺, the recorded neurons were repetitively depolarized from -100 to 0 mV (Lips & Keller, 1999). In the presence of a ‘low Ca²⁺ buffer’ concentration (0.5 mM BAPTA) the prolonged and repetitive depolarization of motoneurons (500 ms, 20 times, 1 Hz) induced: (1) a decrease in the amplitude (to 61 ± 4% mean ± S.E.M.) and (2) a prolongation in the decay kinetics (to 126 ± 9 %) of evoked glycinergic currents (Fig. 1A, B and C). Both effects were reversible; complete recovery was observed within a few minutes. In the presence of an antagonist of CB1 cannabinoid receptors (AM251, 0.5 µM) depolarization-induced depression of glycinergic currents was only to 80% of control, suggesting the involvement of CB1 receptors in the modulation of hypoglossal glycinergic synapses.

Our results demonstrate the presence of a Ca²⁺-dependent modulation of glycinergic synaptic transmission. Further studies have to be carried out for the characterization of the pre- and postsynaptic phenomena involved and to clarify the relationship between this form of modulation and previously described Ca²⁺-dependent fast potentiation of glycine receptor currents.