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KCNQ/Kv7 Channel Regulation of Hippocampal Gamma-Frequency Firing in the Absence of Synaptic Transmission

¹Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol School of Medical Sciences, Bristol; and ²Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, United Kingdom

Submitted 13 October 2005; accepted in final form 2 February 2006

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca²⁺ and raising extracellular K⁺. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ/Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (<0.2 mM) [Ca²⁺]_o and increased (6.3 mM) [K⁺]_o, blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 ± 1.9 mV) depolarizing envelopes with superimposed high-frequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30–80 Hz). Further increasing [K⁺]_o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 µM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991–sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 µM) or XE-991 (10 µM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca²⁺/high K⁺ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.

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