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Potassium voltage-gated channel subfamily KQT member 3 (KQT-like 3) (Potassium channel subunit alpha KvLQT3) (Voltage-gated potassium channel subunit Kv7.3)


Age-dependent modulation of hippocampal excitability by KCNQ-channels.

Recently, mutations of KCNQ2 or KCNQ3, members of the KCNQ-related K( )-channel (KCNQ-channel) family, were identified as cause of benign familial neonatal convulsions (BFNC). However, the exact pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC remain to be elucidated. To clarify the age-dependent etiology of BFNC, we determined age-dependent functional switching of KCNQ-channels, GABAergic- and glutamatergic-transmission in rat hippocampus. The effects of inhibitors of KCNQ-channel, GABA- and glutamate-receptors on propagation of neuronal-excitability and neurotransmitter release were determined by 64-channel multielectrode-dish (MED64), whole-cell recording, in vitro release technique and in vivo microdialysis biosensor, using rat hippocampus from day of birth (P0) to postnatal-day 56 (P56). Inhibition of KCNQ-channels enhanced depolarization-induced glutamate and GABA releases during P0-P7, but not during P14-P28. Inhibition of KCNQ-channels magnified neuronal-excitability propagation from P0 to P14: maximal at P3, but this effect disappeared by P28. GABA(A)-receptor inhibition surprisingly reduced neuronal-excitability propagation during P0-P3, but not at P7. AMPA/glutamate-receptors inhibition reduced propagation of neuronal-excitability throughout the study period. KCNQ-channels inhibition shortened spike-frequency adaptation, but this stimulation was more predominant during P<7 than P>14. During the first week of life, KCNQ-channels performed as a predominant inhibitory system, whereas after this period GABAergic-transmission switched from excitatory to inhibitory function. Contrary, glutamatergic-transmission has acquired as excitatory function from P0. These findings suggest that the pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC are, at least partially, associated with the interaction between age-dependent reduction of inhibitory KCNQ-channel activity and age-dependent functional switching of the GABAergic-system from excitatory to inhibitory action in neonatal CNS.

MeSH Terms

  • Aging
  • Animals
  • Biosensing Techniques
  • Cortical Spreading Depression
  • Epilepsy, Benign Neonatal
  • Glutamic Acid
  • Hippocampus
  • Male
  • Membrane Potentials
  • Microdialysis
  • Neurons
  • Neurotransmitter Agents
  • Potassium
  • Potassium Channels
  • Rats
  • Rats, Wistar
  • Remission, Spontaneous
  • Synaptic Transmission
  • gamma-Aminobutyric Acid

The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3.

Benign familial neonatal convulsions, an autosomal dominant epilepsy of newborns, are linked to mutations affecting two six-transmembrane potassium channels, KCNQ2 and KCNQ3. We isolated four splice variants of KCNQ2 in human brain. Two forms generate, after transient expression in COS cells, a potassium-selective current similar to the KCNQ1 current. L-735,821, a benzodiazepine molecule which inhibits the KCNQ1 channel activity (EC50 = 0.08 microM), also blocks KCNQ2 currents (EC50 = 1.5 microM). Using in situ hybridization, KCNQ2 and KCNQ3 have been localized within the central nervous system, in which they are expressed in the same areas, mainly in the hippocampus, the neocortex and the cerebellar cortex. During brain development, KCNQ3 is expressed later than KCNQ2.

MeSH Terms

  • Aging
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Benzodiazepines
  • Brain
  • COS Cells
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental
  • Genetic Variation
  • Humans
  • In Situ Hybridization
  • KCNQ2 Potassium Channel
  • KCNQ3 Potassium Channel
  • Mice
  • Molecular Sequence Data
  • Organ Specificity
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • RNA, Messenger
  • Recombinant Proteins
  • Transcription, Genetic
  • Transfection