Abstract

Exploring the principles that govern activity-dependent changes in excitability is an essential step to understand the function of the nervous system, because they act as a general postsynaptic control mechanism that modulates the flow of synaptic signals. We show an activity-dependent potentiation of the slow Ca2+-activated K+ current (sI(AHP)) which induces sustained decreases in the excitability in CA1 pyramidal neurons. We analyzed the sI(AHP) using the slice technique and voltage-clamp recordings with sharp or patch-electrodes. Using sharp electrodes-repeated activation with depolarizing pulses evoked a prolonged (8-min) potentiation of the amplitude (171%) and duration (208%) of the sI(AHP). Using patch electrodes, early after entering the whole-cell configuration (< 20 min), responses were as those reported above. However, although the sI(AHP) remained unchanged, its potentiation was markedly reduced in later recordings, suggesting that the underlying mechanisms were rapidly eliminated by intracellular dialysis. Inhibition of L-type Ca2+ current by nifedipine (20 ?M) markedly reduced the sI(AHP) (79%) and its potentiation (55%). Ryanodine (20 ?M) that blocks the release of intracellular Ca2+ also reduced sI(AHP) (29%) and its potentiation (25%). The potentiation of the sI(AHP) induced a marked and prolonged (> 50%; approximate 8 min) decrease in excitability. The results suggest that sI(AHP) is potentiated as a result of an increased intracellular Ca2+ concentration ([Ca2+](i)) following activation of voltage-gated L-type Ca2+ channels, aided by the subsequent release of Ca2+ from intracellular stores. Another possibility is that repeated activation increases the Ca2+-binding capacity of the channels mediating the sI(AHP). This potentiation of the sI(AHP) could be relevant in hippocampal physiology, because the changes in excitability it causes may regulate the induction threshold of the long-term potentiation of synaptic efficacy. Moreover, the potentiation would act as a protective mechanism by reducing excitability and preventing the accumulation of intracellular Ca2+ to toxic levels when intense synaptic activation occurs. (C) 2000 Wiley-Liss, Inc.