Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents
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Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents. / Meehan, Claire Francesca; Moldovan, Mihai; Marklund, Stefan L.; Graffmo, Karin S.; Nielsen, Jens Bo; Hultborn, Hans.
In: Acta Physiologica (Print Edition), Vol. 200, No. 4, 2010, p. 361-376.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents
AU - Meehan, Claire Francesca
AU - Moldovan, Mihai
AU - Marklund, Stefan L.
AU - Graffmo, Karin S.
AU - Nielsen, Jens Bo
AU - Hultborn, Hans
N1 - CURIS 2010 5200 130
PY - 2010
Y1 - 2010
N2 - Aim: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a preferential loss of motoneurones. Previous publications using in vitro neonatal preparations suggest an increased excitability of motoneurones in various superoxide dismutase-1 (SOD1) mutant mice models of ALS which may contribute to excitotoxicity of the motoneurones. Methods: Using intracellular recording we tested this hypothesis in vivo in the adult presymptomatic G127insTGGG (G127X) SOD1 mutant mouse model of ALS. Results: At resting membrane potentials the basic intrinsic properties of lumbar motoneurones in the adult presymptomatic G127X mutant are not significantly different from those of wild type. However, at more depolarized membrane potentials, motoneurones in the G127X SOD1 mutants can sustain higher frequency firing, showing less spike frequency adaption and with persistent inward currents (PICs) being activated at lower firing frequencies and being more pronounced. Conclusion: We demonstrated that, in vivo, at resting membrane potential, spinal motoneurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence of an increased PIC and less spike frequency adaptation which may contribute to excitotoxity of these neurones as the disease progresses.
AB - Aim: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a preferential loss of motoneurones. Previous publications using in vitro neonatal preparations suggest an increased excitability of motoneurones in various superoxide dismutase-1 (SOD1) mutant mice models of ALS which may contribute to excitotoxicity of the motoneurones. Methods: Using intracellular recording we tested this hypothesis in vivo in the adult presymptomatic G127insTGGG (G127X) SOD1 mutant mouse model of ALS. Results: At resting membrane potentials the basic intrinsic properties of lumbar motoneurones in the adult presymptomatic G127X mutant are not significantly different from those of wild type. However, at more depolarized membrane potentials, motoneurones in the G127X SOD1 mutants can sustain higher frequency firing, showing less spike frequency adaption and with persistent inward currents (PICs) being activated at lower firing frequencies and being more pronounced. Conclusion: We demonstrated that, in vivo, at resting membrane potential, spinal motoneurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence of an increased PIC and less spike frequency adaptation which may contribute to excitotoxity of these neurones as the disease progresses.
U2 - 10.1111/j.1748-1716.2010.02188.x
DO - 10.1111/j.1748-1716.2010.02188.x
M3 - Journal article
C2 - 20874803
VL - 200
SP - 361
EP - 376
JO - Acta Physiologica
JF - Acta Physiologica
SN - 1748-1708
IS - 4
ER -
ID: 22454601