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. 1996 Oct 15;496(Pt 2):395–405. doi: 10.1113/jphysiol.1996.sp021693

Temporal specificity of muscarinic synaptic modulation of the Ca(2+)-dependent K+ current (ISAHP) in rat hippocampal neurones.

L Zhang 1, D Han 1, P L Carlen 1
PMCID: PMC1160885  PMID: 8910224

Abstract

1. We examined synaptic modulation of the Ca(2+)-dependent K+ current (ISAHP), which underlies the slow after-hyperpolarization (sAHP) in hippocampal CA1 neurones of rat brain slices. ISAHP was evoked in whole-cell voltage-clamp mode by depolarizing pulses, and synaptic afferents to CA1 neurones were stimulated electrically with a paired-pulse protocol. 2. Afferent stimulation delivered 200-1500 ms prior to be depolarizing pulse produced a profound reduction of ISAHP by 58%, but not other Ca(2+)-dependent outward currents that preceded ISAHP. Perfusion of slices with atropine significantly attenuated the synaptic reduction of ISAHP, indicating an event mediated largely by muscarinic receptor activation. When delivered < 400 ms after the depolarizing pulse, similar synaptic stimuli produced no substantial reduction in ISAHP, even in neurons where the duration of ISAHP was prolonged to 8-10 s either by lowering the recording temperature or by intracellular application of a calcium chelator. 3. To examine the effect of cholinergic stimulation of the depolarization-activated Ca2+ influx, high-threshold voltage-activated Ca2+ currents were recorded in the conventional or perforated whole-cell mode. Perfusion of slices with 5-10 microM carbachol for 5-10 min caused no substantial decrease in these Ca2+ currents, suggesting that the synaptic reduction of ISAHP is unlikely to be due to a blockade of depolarization-induced Ca2+ influx which triggers the generation of ISAHP. 4. The present data demonstrate that afferent stimulation reduces ISAHP only if it occurs prior to the depolarization-induced Ca2+ influx. We propose that modulation of inactive sAHP channels by muscarinic stimulation may decrease their sensitivity to the influx of Ca2+, whereas sAHP channels activated by Ca2+ may compete with the receptor-coupled modulation thus rendering the sAHP channels unresponsive to cholinergic afferent stimulation.

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Selected References

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