Intrinsic membrane properties of locus coeruleus neurons in Mecp2-null mice.
Rett syndrome caused by mutations in methyl-CpG-binding protein 2 (Mecp2) gene shows abnormalities in autonomic functions in which brain stem norepinephrinergic systems play an important role. Here we present systematic comparisons of intrinsic membrane properties of locus coeruleus (LC) neurons between Mecp2(-/Y) and wild-type (WT) mice. Whole cell current clamp was performed in brain slices of 3- to 4-wk-old mice. Mecp2(-/Y) neurons showed stronger inward rectification and had shorter time constant than WT cells. The former was likely due to overexpression of inward rectifier K(+) (K(ir))4.1 channel, and the latter was attributable to the smaller cell surface area. The action potential duration was prolonged in Mecp2(-/Y) cells with an extended rise time. This was associated with a significant reduction in the voltage-activated Na(+) current density. After action potentials, >60% Mecp2(-/Y) neurons displayed fast and medium afterhyperpolarizations (fAHP and mAHP), while nearly 90% WT neurons showed only mAHP. The mAHP amplitude was smaller in Mecp2(-/Y) neurons. The firing frequency was higher in neurons with mAHP, and the frequency variation was greater in cells with both fAHP and mAHP in Mecp2(-/Y) mice. Small but significant differences in spike frequency adaptation and delayed excitation were found in Mecp2(-/Y) neurons. These results indicate that there are several electrophysiological abnormalities in LC neurons of Mecp2(-/Y) mice, which may contribute to the dysfunction of the norepinephrine system in Rett syndrome.
Zhang
Xiaoli
X
Dept. of Biology, Georgia State Univ., 24 Peachtree Center Ave., Atlanta, GA 30303, USA.
Cui
Ningren
N
Wu
Zhongying
Z
Su
Junda
J
Tadepalli
Jyothirmayee S
JS
Sekizar
Sowmya
S
Jiang
Chun
C
D000200:Action Potentials; D000320:Adrenergic Fibers / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D017097:Electric Impedance; D066298:In Vitro Techniques; D007700:Kinetics; D008125:Locus Coeruleus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D000098854:Kcnj10 Channel
D000098854:Kcnj10 Channel; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D024661:Potassium Channels, Inwardly Rectifying; C568249:Scn1a protein, mouse; D015222:Sodium Channels; D012964:Sodium; D011188:Potassium; D009638:Norepinephrine