Abstract
Several mutations of KCNQ2 and KCNQ3 are considered to be associated with benign familial neonatal convulsions (BFNC).
BFNC is characterized by seizures starting within several days of life and spontaneous
remission within weeks to months. KCNQ channel is a heteromeric voltage-dependent
potassium channel consisting of KCNQ2 and KCNQ3 subunits. To clarify the age-dependent
etiology of BFNC, we examined the developmental changes in KCNQ2 and KCNQ3 expression
in human hippocampus, temporal lobe, cerebellum and medulla oblongata obtained from
23 subjects who died at 22 gestation weeks to adulthood. Formalin-fixed and paraffin-embedded
specimens were used for immunohistochemistry. Unique developmental changes in KCNQ2
and KCNQ3 were found in each region. A high expression of KCNQ2 was identified in
the hippocampus, temporal cortex, cerebellar cortex and medulla oblongata in fetal
life, but such expression decreased after birth. The expression of KCNQ3 increased
in late fetal life to infancy. Simultaneous and high expressions of KCNQ2 and KCNQ3
were observed in each region from late fetal life to early infancy, coinciding with
the time when BFNC occurs. Such coexpression may contribute to the pathogenesis of
BFNC.
Keywords
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References
- A novel mutation of KCNQ3 (c.925T–>C) in a Japanese family with benign familial neonatal convulsions.Ann Neurol. 2000; 47: 822-826
- Are some idiopathic epilepsies disorders of ion channels?: A working hypothesis.Epilepsy Res. 2000; 41: 191-204
- Benign familial neonatal convulsions: generalized epilepsy?.Pediatr Neurol. 1992; 8: 226-228
- Neonate with benign familial neonatal convulsions: recorded generalized and focal seizures.Pediatr Neurol. 1994; 10: 164-165
- A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsions.Ann Neurol. 1999; 46: 305-312
- A potassium channel mutation in neonatal human epilepsy.Science. 1998; 279: 403-406
- A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.Nat Genet. 1998; 18: 53-55
- A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.Nat Genet. 1998; 18: 25-29
- Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone.Nature. 1980; 283: 673-676
- Voltage-clamp analysis of muscarinic excitation in hippocampal neurons.Brain Res. 1982; 250: 71-92
- Control of M-current.Annu Rev Physiol. 1997; 59: 483-504
- KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.Science. 1998; 282: 1890-1893
- Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy.Nature. 1998; 396: 687-690
- The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3.FEBS Lett. 1998; 438: 171-176
- Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.Proc Natl Acad Sci USA. 2000; 97: 4914-4919
- M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain.J Neurosci. 2001; 21: 9529-9540
- Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.J Biol Chem. 1998; 273: 19419-19423
- Differential expression of KCNQ2 splice variants: implications to M current function during neuronal development.J Neurosci. 2001; 21: 1096-1103
- KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents.J Biol Chem. 2000; 275: 24089-24095
- Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy.J Biol Chem. 2000; 275: 13343-13348
- Lissencephaly gene product. Localization in the central nervous system and loss of immunoreactivity in Miller–Dieker syndrome.Am J Pathol. 1995; 147: 1142-1151
- Immunohistochemical analysis of KCNQ2 potassium channels in adult and developing mouse brain.Brain Res. 2006; 1077: 1-6
- Immunohistochemical analysis of KCNQ3 potassium channels in mouse brain.Neurosci Lett. 2006; 400: 101-104
- Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior.Nat Neurosci. 2005; 8: 51-60
- Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current.J Neurosci. 2000; 20: 1710-1721
- International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function.Pharmacol Rev. 1998; 50: 291-313
- Excitatory GABA responses in embryonic and neonatal cortical slices demonstrated by gramicidin perforated-patch recordings and calcium imaging.J Neurosci. 1996; 16: 6414-6423
- GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition.Cell. 2001; 105: 521-532
- Age-dependent modulation of hippocampal excitability by KCNQ-channels.Epilepsy Res. 2003; 53: 81-94
- Development of hyperpolarizing inhibitory postsynaptic potentials and hyperpolarizing response to gamma-aminobutyric acid in rabbit hippocampus studied in vitro.J Neurosci. 1984; 4: 860-867
- Giant synaptic potentials in immature rat CA3 hippocampal neurones.J Physiol. 1989; 416: 303-325
- Postnatal maturation of the GABAergic system in rat neocortex.J Neurophysiol. 1991; 65: 247-263
- Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices.J Physiol. 1991; 444: 25-49
- Developmental changes in the expression of GABA(A) receptor alpha 1 and gamma 2 subunits in human temporal lobe, hippocampus and basal ganglia: An implication for consideration on age-related epilepsy.Epilepsy Res. 2006; 71: 47-53
Article info
Publication history
Accepted:
November 8,
2007
Received in revised form:
October 30,
2007
Received:
March 27,
2007
Identification
Copyright
© 2007 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
