Mechanisms underlying activation of the slow AHP in rat hippocampal neurons

The firing of a train of action potentials in hippocampal pyramidal neurons is terminated by an afterhyperpolarization (AHP) that displays two main components; the medium AHP (ImAHP), lasting a few hundred milliseconds and the slow AHP (IsAHP), that has a duration of several seconds. It is unclear how much of ImAHP is dependent on the entry of calcium ions (Ca2+), whereas it is accepted that IsAHP is caused by activation of Ca2+-activated potassium channels. There has been controversy regarding the subcellular localization and mechanism of activation of these channels. Whole-cell recordings from CA1 neurons in the hippocampal slice preparation showed that inhibition of L-type, but not N-, P/Q-, T- and R-type Ca2+ channels, reduced both ImAHP and IsAHP. Inhibition of both AHP components by L-type Ca2+ channel antagonists was not complete, with IsAHP being significantly more sensitive than ImAHP. Somatic extracellular ionophoresis of BAPTA during IsAHP caused a transient inhibition, but had no effect on ImAHP. Cell-attached patch recordings from the soma of CA1 neurons within a slice displayed channels that produced an ensemble waveform reminiscent of IsAHP when the patch was subjected to a train of action potential waveforms. The channels were Ca2+-activated, exhibited a limiting slope conductance of 19 pS and were not observed in dendritic membrane patches. These data demonstrate that the IsAHP is somatic in origin and arises from continued Ca2+ entry through functionally co-localized L-type channels.