Acidosis of rat dorsal vagal neurons in situ during spontaneous and evoked activity.

Trapp, Stefan; Lückermann, Mark; Brooks, P. A.; Ballanyi, Klaus

doi:10.1113/jphysiol.1996.sp021720

Cited by 66 publications

(54 citation statements)

References 35 publications

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“…Various depolarizing stimuli are also known to cause an influx in Ca 2ϩ that is also accompanied by a significant decrease in pH i in hippocampal neurons as well as other nerve cells, followed by active extrusion of excess H ϩ over several minutes to restore pH i (87)(88)(89)(90)(91)(92)(93). More recently, Diering and colleagues (25) extended these observations by showing that NMDA receptor-induced neural activity initiates a modest acidification of dendritic spines (i.e.…”

Section: Discussionmentioning

confidence: 97%

Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface

Jinadasa

Szabó

Numata

et al. 2014

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 97%

Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface

Jinadasa

Szabó

Numata

et al. 2014

Journal of Biological Chemistry

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“…K ATP may be activated by lactoacidosis during skeletal muscle fatigue (31), contributing to the decrease in tetanic force and the protection against injury (3). Excessive neuronal activity also reduces pH i (32), which may activate the K ATP , leading to a suppression of hyperexcitability and a cessation of seizure activity (2). Therefore, the demonstration of K ATP modulation by pH i has a profound impact on understanding cellular functions during metabolic stress and offers a potential intervention to control the cellular activity by manipulating the inherent pH sensing mechanism of the K ATP channels in the treatment and prevention of stroke, epilepsy, diabetes mellitus, and coronary heart diseases.…”

Section: Figmentioning

confidence: 99%

Direct Activation of Cloned KATP Channels by Intracellular Acidosis

Xu¹,

Cui²,

Yang

et al. 2001

Journal of Biological Chemistry

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ATP-sensitive K؉ (K ATP ) channels may be regulated by protons in addition to ATP, phospholipids, and other nucleotides. Such regulation allows a control of cellular excitability in conditions when pH is low but ATP concentration is normal. However, whether the K ATP changes its activity with pH alterations remains uncertain. In this study we showed that the reconstituted K ATP was strongly activated during hypercapnia and intracellular acidosis using whole-cell recordings. Further characterizations in excised patches indicated that channel activity increased with a moderate drop in intracellular pH and decreased with strong acidification. The channel activation was produced by a direct action of protons on the Kir6 subunit and relied on a histidine residue that is conserved in all K ATP . The inhibition appeared to be a result of channel rundown and was not seen in whole-cell recordings. The biphasic response may explain the contradictory pH sensitivity observed in cell-endogenous K ATP in excised patches. Site-specific mutations of two residues showed that pH and ATP sensitivities were independent of each other. Thus, these results demonstrate that the proton is a potent activator of the K ATP . The pH-dependent activation may enable the K ATP to control vascular tones, insulin secretion, and neuronal excitability in several pathophysiologic conditions. Hypercapnia and acidosis affect vascular tone, skeletal muscle contractility, insulin secretion, epithelial transport, and neuronal excitability, which may be mediated by K ATP 1 (1-5). However, previous studies on the pH sensitivity of these K ϩ channels were controversial and even contradictory. In the absence of ATP, acidic pH was shown to stimulate cell-endogenous K ATP (6, 7), inhibit it (8, 9), and have little or no effect (10, 11). This inconsistency is further complicated by the indirect effect of ATP or Mg 2ϩ and tissue-specific K ATP species (8 -12). Consequently, it is unclear whether K ATP is modulated during hypercapnia and acidosis and what molecular mechanisms are underlying the modulations. The cloned K ATP channels are ideal for addressing these questions because they allow for fine dissection of the modulatory mechanisms and elaborate manipulation of PCO 2 and pH in an expression system (13,14). Therefore, we studied the modulation of the cloned K ATP (Kir6 with SUR, Ref. 15) by CO 2 and acidic pH. To locate the pH sensors, we also studied Kir6.2 with a truncation of 36 amino acids at the C terminus (Kir6.2⌬C36) because it expresses functional channel without the SUR subunit and retains fair ATP sensitivity (16). MATERIALS AND METHODSOocytes from Xenopus laevis were used in the present studies. Frogs were anesthetized by bathing them in 0.3% 3-aminobenzoic acid ethyl ester. A few lobes of ovaries were removed after a small abdominal incision (ϳ5 mm). Then, the surgical incision was closed and the frogs were allowed to recover from the anesthesia. Xenopus oocytes were treated with 2 mg/ml collagenase (Type I, Sigma) in an OR2 solution consistin...

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“…The majority of the in vitro experimental investigations, however, have been conducted on coronal brainstem slices [5][6][7]20,22,23,25].…”

Section: Introductionmentioning

confidence: 99%

Morphological differences between planes of section do not influence the electrophysiological properties of identified rat dorsal motor nucleus of the vagus neurons

2004

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Recent cytoarchitectonic studies have shown that the dorsal motor nucleus of the vagus (DMV) comprises neurons with different morphological features. Our own studies, conducted in horizontal brainstem slices, have shown that DMV neurons projecting to stomach areas can be distinguished from neurons projecting to the intestine on the basis of their electrophysiological as well as morphological properties. The majority of the in vitro experimental investigations, however, have been conducted on coronal brainstem slices. The aim of the present study was to assess whether the electrophysiological properties of DMV neurons are due to intrinsic membrane properties of the neurons or are dependent upon the plane of section, i.e., coronal vs. horizontal, in which the brainstem is cut. The fluorescent retrograde tracer DiI was applied to either the stomach or intestine of rats. Whole cell recordings were subsequently made from labeled DMV neurons in thin brainstem slices sectioned in either the horizontal or coronal plane. In the horizontal plane, both the somata and the dendritic tree of gastric-projecting neurons were smaller than intestinalprojecting neurons. In the coronal plane, however, apart from a smaller soma diameter in gastricprojecting neurons, morphological differences were not found between the groups. The electrophysiological differences observed between the groups were, however, consistent in both planes of section, that is, intestinal-projecting neurons had larger and longer afterhyperpolarization (AHP) as well as slower frequency-responses to depolarizing stimuli than gastric-projecting neurons. Our data suggest that intrinsic rather than morphological features govern the electrophysiological characteristics of DMV neurons.

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Acidosis of rat dorsal vagal neurons in situ during spontaneous and evoked activity.

Abstract: 1. Rat brainstem slices were taken for simultaneous measurements of intracellular pH (pHi) and membrane currents

Cited by 66 publications

References 35 publications

Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface

Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface

Direct Activation of Cloned KATP Channels by Intracellular Acidosis

Morphological differences between planes of section do not influence the electrophysiological properties of identified rat dorsal motor nucleus of the vagus neurons

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