The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells

1. The role of large-conductance Ca2+-dependent Kf channels (BK-channels; a lso known as maxi-K- or slo-channels) in spike broadening during repetitive firing was studied in CA1 pyramidal cells, using sharp electrode intracell ular recordings in rat hippocampal slices, and computer modelling. 2. Trains of action potentials elicited by depolarizing current pulses show ed a progressive, frequency-dependent spike broadening, reflecting a reduce d rate of repolarization. During a 50 ms long 5 spike train, the spike dura tion increased by 63.6 +/- 3.4% from the Ist to the 3rd spike. The amplitud e of the fast after-hyperpolarization (fAHP) also rapidly declined during e ach train. 3. Suppression of BK-channel activity with (a) the selective BK-channel blo cker iberiotoxin (IbTX, 60 nM), (b) the non-peptidergic BK-channel blocker paxilline (2-10 mu M), or (c) calcium-free medium, broadened the Ist spike to a similar degree (similar to 60%). BK-channel suppression also caused a similar change in spike waveform as observed during repetitive firing, and eliminated (occluded) most of the spike broadening during repetitive firing . 4. Computer simulations using a reduced compartmental model with transient BK-channel current and 10 other active ionic currents, produced an activity -dependent spike broadening that was strongly reduced when the BK-channel i nactivation mechanism was removed. 5. These results, which are supported by recent voltage-clamp data, strongl y suggest that in CA1 pyramidal cells, fast inactivation of a transient BK- channel current (I-CT), substantially contributes to frequency-dependent sp ike broadening during repetitive firing.