Voltage dependence of the glycine receptor-channel kinetics in the zebrafish hindbrain

Electrophysiological recordings of outside-out patches to fast-flow applica tions of glycine were made on patches derived from the Mauthner cells of th e 50-h-old zebrafish larva. As for glycinergic miniature inhibitory postsyn aptic currents (mIPSCs), depolarizing the patch produced a broadening of th e transient outside-out current evoked by short applications (1 ms) of a sa turating concentration of glycine (3 mM). When the outside-out patch was de polarized from -50 to +20 mV, the peak current varied linearly with voltage . A I-ms application of 3 mM glycine evoked currents that activated rapidly and deactivated biexponentially with time constants of approximate to 5 an d approximate to 30 ms (holding potential of -50 mV). These two decay time constants were increased by depolarization. The fast deactivation time cons tant increased e-fold per 95 mV. The relative amplitude of the two decay co mponents did not significantly vary with voltage. The fast component repres ented 64.2 +/- 2.8% of the total current at -50 mV and 54.1 +/- 10% at +20 mV. The 20-80% rise time of these responses did not show any voltage depend ence, suggesting that the opening rate constant is insensitive to voltage. The 20-80% rise time was 0.2 ms at -70 mV and 0.22 ms at +20 mV. Responses evoked by 100-200 ms application of a low concentration of glycine (0.1 mM) had a biphasic rising phase reflecting the complex gating behavior of the glycine receptor. The time constant of these two components and their relat ive amplitude did not change with voltage, suggesting that modal shifts in the glycine-activated channel gating mode are not sensitive to the membrane potential. Using a Markov model to simulate glycine receptor gating behavi or, we were able to mimic the voltage-dependent change in the deactivation time course of the responses evoked by I-ms application of 3 mM glycine. Th is kinetics model incorporates voltage-dependent closing rate constants. It provides a good description of the time course of the onset of responses e voked by the application of a low concentration of glycine at all membrane potentials tested.