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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)
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)
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)
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)
Rett syndrome is a neurodevelopmental disorder caused by Mecp2 gene mutations. In RTT patients and Mecp2-null (Mecp2(-/Y)) mice, norepinephrine (NE) content drops significantly, which may play a role in breathing arrhythmia, sleep disorders and sudden death. However, the underlying mechanisms for the NE defect are not fully understood. The NE defect may(More)
Heteromultimerization of Kir4.1 and Kir5.1 leads to a channel with distinct functional properties. The heteromeric Kir4.1-Kir5.1 channel is expressed in the eye, kidney and brainstem and has CO(2)/pH sensitivity in the physiological range, suggesting a candidate molecule for the regulation of K(+) homeostasis and central CO(2) chemoreception. It is known(More)
CO(2) is an important metabolic product whose concentrations are constantly monitored by CO(2) chemoreceptors. However, the high systemic CO(2) sensitivity may not be achieved by the CO(2) chemoreceptors without neuronal network processes. To show modulation of network properties during hypercapnia, we studied brainstem neurons dissociated from embryonic(More)
The adenosine triphosphate-sensitive K(+) (K(ATP)) channels are gated by several metabolites, whereas the gating mechanism remains unclear. Kir6.2, a pore-forming subunit of the K(ATP) channels, has all machineries for ligand binding and channel gating. In Kir6.2, His175 is the protonation site and Thr71 and Cys166 are involved in channel gating. Here, we(More)
The Kv4.2 gene codes for an essential subunit of voltage-gated A-type potassium channels that are involved in dendritic signal integration and synaptic plasticity. Detailed cellular characterization in CA1 pyramidal neurons of the hippocampus has shown that knocking out the Kv4.2 gene increases neuronal excitability and promotes long-term potentiation.(More)
The heteromeric Kir4.1-Kir5.1 channel is a candidate sensing molecule for central CO(2) chemoreception. Since central CO(2) chemoreception is subject to neural modulations, we performed studies to test the hypothesis that the Kir4.1-Kir5.1 channel is modulated by the neurotransmitters critical for respiratory control, including serotonin (5-HT), substance-P(More)