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Temporal specificity of muscarinic synaptic modulation of the Ca(2+)‐dependent K+ current (ISAHP) in rat hippocampal neurones.
Author(s) -
Zhang L,
Han D,
Carlen P L
Publication year - 1996
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1996.sp021693
Subject(s) - depolarization , neuroscience , hyperpolarization (physics) , chemistry , stimulation , carbachol , muscarinic acetylcholine receptor , hippocampal formation , biophysics , biology , receptor , biochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
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.