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People with Rett syndrome (RTT) have breathing instability in addition to other neuropathological manifestations. The breathing disturbances contribute to the high incidence of unexplained death and abnormal brain development. However, the cellular mechanisms underlying the breathing abnormalities remain unclear. To test the hypothesis that the central(More)
CO2 chemoreception may be related to modulation of inward rectifier K+ channels (Kir channels) in brainstem neurons. Kir4.1 is expressed predominantly in the brainstem and inhibited during hypercapnia. Although the homomeric Kir4.1 only responds to severe intracellular acidification, coexpression of Kir4.1 with Kir5.1 greatly enhances channel sensitivities(More)
The inward rectifier K(+) channels function in the regulation of myocardial rhythmicity, vascular tones, epithelial transport, and neuronal excitability. Most of these channels are gated by pH. It is now known that the gating process involves a large number of protein domains and amino acid residues in both N- and C-termini of the channel protein.(More)
Kir1.1 channel regulates membrane potential and K+ secretion in renal tubular cells. This channel is gated by intracellular protons, in which a lysine residue (Lys80) plays a critical role. Mutation of the Lys80 to a methionine (K80M) disrupts pH-dependent channel gating. To understand how an individual subunit in a tetrameric channel is involved in(More)
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(More)
Synaptic cleft acidification occurs following vesicle release. Such a pH change may affect synaptic transmissions in which G-protein-coupled inward rectifier K(+) (GIRK) channels play a role. To elucidate the effect of extracellular pH (pH(o)) on GIRK channels, we performed experiments on heteromeric GIRK1/GIRK4 channels expressed in Xenopus oocytes. A(More)
CO2 central chemoreceptors play an important role in cardiorespiratory control. They are highly sensitive to P(CO2) in a broad range. These two sensing properties seem paradoxical as none of the known pH-sensing molecules can achieve both. Here we show that cultured neuronal networks are likely to solve the sensitivity versus spectrum problem with parallel(More)
A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on(More)
Rett syndrome (RTT) is a neurodevelopmental disorder with symptoms starting 6-18 mo after birth, while what underlies the delayed onset is unclear. Allopregnanolone (Allop) is a metabolite of progesterone and a potent modulator of GABAA-ergic currents whose defects are seen in RTT. Allop changes its concentration during the perinatal period, which may(More)
G-protein-coupled inward rectification K(+) (GIRK) channels play an important role in modulation of synaptic transmission and cellular excitability. The GIRK channels are regulated by diverse intra- and extracellular signaling molecules. Previously, we have shown that GIRK1/GIRK4 channels are activated by extracellular protons. The channel activation(More)