KCNQ/M channels control spike afterdepolarization and burst generation in hippocampal neurons - PubMed (original) (raw)

Comparison of the effects of blockers of different K+ channels on spike waveform in CA1 pyramidal cells. A, Effects of paxilline. Top, Overlay of intracellular recordings of spikes evoked in control ASCF (solid line), 30 min after adding 10 μ

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paxilline (dotted line) and 20 min after adding 10 μ

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linopirdine to the paxilline-containing ACSF (dashed line). Paxilline had no detectible effect on the spike ADP, whereas linopirdine enhanced the ADP to the point of bursting. Bottom, Data are the same as above, but at an expanded time scale, showing spike broadening by paxilline. B, Effects of iberiotoxin. Recordings from another neuron in control ASCF (solid line), 30 min after adding 100 n

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iberiotoxin to the ACSF (dotted line) and 25 min after adding 10 μ

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linopirdine to the iberiotoxin-containing ACSF (dashed line). Iberiotoxin blocked the fAHP but had no visible effect on the spike ADP, whereas linopirdine enhanced the ADP to the point of bursting. Bottom, Expanded traces showing attenuation of spike repolarization by iberiotoxin. C, Effects of apamin. Recordings from another neuron in control ASCF (solid line), 30 min after adding 50 n

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apamin to the ACSF (dotted line) and 30 min after adding 10 μ

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linopirdine to the apamin-containing ACSF (dashed line). Apamin did not affect the spike ADP, whereas linopirdine induced an intense burst response. Bottom, Expanded traces showing that apamin does not affect spike repolarization. D, Effects of bicuculline. Recordings from another neuron in control ASCF (solid line),30 min after adding 10 μ

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bicuculline methiodide to the ACSF (dotted line) and 30 min after adding 10 μ

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linopirdine to the bicuculline-containing ACSF (dashed line). Bicuculline slightly augmented the spike ADP, whereas linopirdine facilitated it to the point of bursting. Bottom, Expanded traces showing that bicuculline markedly attenuates spike repolarization, and this effect was further enhanced by linopirdine. E, Effects of 4-AP. Recordings from another neuron in control ASCF (solid line), 30 min after adding 100 μ

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4-AP to the ACSF (dotted line) and 20 min after adding 10 μ

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linopirdine to the 4-AP-containing ACSF (dashed line). The spike ADP was not affected by 4-AP, whereas linopirdine induced a burst response. Bottom, Expanded traces showing that no effect of 4-AP on fast spike repolarization. F-G, Bar diagrams summarizing the effects of the seven K+ channel blockers on spike width (expressed as percentage of control), fAHP (expressed as absolute change in millivolts), and spike ADP size (expressed as percentage of control), respectively. Each bar represents the change in spike parameter after 30 min of exposure to a drug. The number of neurons in each of the five experimental groups was 20 (linopirdine), 7 (XE991), 7 (paxilline), 7 (iberiotoxin), 5 (apamin), 5 (bicuculline), and 6 (4-AP). The asterisks above the bars denote that the observed changes were statistically significant.