Reduced outward K⁺ conductances generate depolarizing after–potentials in rat supraoptic nucleus neurones

Abstract

Whole‐cell patch clamp recordings were obtained from sixty‐five rat supraoptic nucleus (SON) neurones in brain slices to investigate ionic mechanisms underlying depolarizing after‐potentials (DAPs). When cells were voltage clamped around ‐58 mV, slow inward currents mediating DAPs (Idap), evoked by three brief depolarizing pulses, had a peak of 17 ± 1 pA (mean ± s.e.m.) and lasted for 2.8 ± 0.1 s. No significant differences in the amplitude and duration were observed when one to three preceding depolarizing pulses were applied, although there was a tendency for twin pulses to evoke larger Idap than a single pulse. The Idap was absent when membrane potentials were more negative than ‐70 mV. In the range ‐70 to ‐50 mV, Idap amplitudes and durations increased as the membrane became more depolarized, with an activation threshold of ‐65.7 ± 0.7 mV. I dap with normal amplitude and duration could be evoked during the decay of a preceding Idap. As frequencies of depolarizing pulses rose from 2 to 20 Hz, the times to peak Idap amplitude were reduced but the amplitudes and durations did not change. A consistent reduction in membrane conductance during the Idap was observed in all SON neurones tested, and averaged 34.6 ± 3.3%. Small hyperpolarizing pulses used to measure membrane conductances appeared not to disturb major ionic mechanisms underlying Idap, since the slope and duration of Idap with and without test pulses were similar. The Idap had an averaged reversal potential of ‐87.4 ± 1.6 mV, which was close to the K+ equilibrium potential. An elevation in [K+]O reduced or abolished the Idap, and shifted its reversal potential toward more positive levels. Perifusion of slices with 7.5–10 mm TEA, a K+ channel blocker, reversibly suppressed the Idap. Both Na+ and Ca2+ currents failed to induce an Idap‐like current during perifusion of slices with media containing high [K+]o or TEA. However, the Idap was abolished by replacing external Ca2+ with Co2+, or replacing 82% of external Na+ with choline or Li+. Perifusion of slices with media containing 1–2 μm TTX also reduced Idap by 55.5 ± 9.0 %. These results suggest that the generation of DAPs in SON neurones mainly involves a reduction in outward K+ current(s), which probably has little or no inactivation and can be inhibited by [Ca2+]i transients, due to Ca2+ influx during action potentials and Ca2+ release from internal stores. Na+ influx might provide a permissive influence for Ca2+‐induced reduction of K+ conductances and/or help to raise [Ca2+]i via reverse‐mode Ca2+‐Na+ exchange. Other conductances, making minor contributions to the Idap, may also be involved.

Physiologic Regulation of a Tetrodotoxin-Sensitive Sodium Influx That Mediates a Slow Afterdepolarization Potential in Gonadotropin-Releasing Hormone Neurons: Possible Implications for the Central Regulation of Fertility

“…4 A, 5F ). An sADP with similar kinetics is observed in magnocellular neuroendocrine neurons Dudek, 1983, 1984;Li and Hatton, 1996); it has been proposed that a reduction in outward TEAsensitive I K generates this sADP (Li and Hatton, 1997b). The sADP of GnRH neurons, however, was not affected by TEA (n ϭ 7) (Figs.…”

Somato-dendritic mechanisms underlying the electrophysiological properties of hypothalamic magnocellular neuroendocrine cells: A multicompartmental model study

“…Since CAN channel activation depends on intracellular [Ca 2+ ], the distribution of g CAN between model compartments may have a significant influence on the DAP. The values of g CAN,s =45 μS/cm 2 , g CAN,pd =90 μS/cm 2 and g CAN,sd =0 provided the best correspondence between simulated and experimental data (Bourque 1986;Li and Hatton 1997b) (Fig. 7(a-d)).…”

Muscarinic Receptor Modulation of Slow Afterhyperpolarization and Phasic Firing in Rat Supraoptic Nucleus Neurons

“…We therefore examined the effects of muscarinic receptor activation on these parameters. Because plateau potentials are activity and voltage dependent (Bourque, 1986;Li and Hatton, 1997), individual trials were evoked at intervals of Ͼ20 sec and from a constant baseline voltage near Ϫ55 mV. As illustrated in Figure 6 A, bath application of muscarine reversibly enhanced the duration of the afterdischarge.…”