KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission

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 mu M), a Kv7 channel modulator, completely abolished the bursts, in an XE-991 - sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine ( 10 mu M) or XE-991 ( 10 mu M) 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.