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 microM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991-sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 microM) or XE-991 (10 microM) 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.
Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol School of Medical Sciences, Bristol, UK.
S
S
Piccinin
A D
AD
Randall
J T
JT
Brown
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010507:Periodicity; D010655:Phenylenediamines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*
C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D002219:Carbamates; D007211:Indoles; D051656:KCNQ Potassium Channels; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D011725:Pyridines; C101866:ezogabine; C061017:linopirdine; D011188:Potassium; D002118:Calcium