Alkalosis leads to the over-activity of cortical principal neurons

Lu, Yunting; Yi, Lian; Liu, Danian; Li, Jinlong; Sun, Ling; Zhang, Zhongling

doi:10.1016/j.neulet.2012.07.034

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…Our cases, as well as those previously reported ( Barker et al, 2012 ), confirm that in some individuals HV can cause HIHARSAA and suggest that alkalosis is the core of HIHARSAA-associated biochemical mechanism ( Schuchmann et al, 2009 , Lu et al, 2012 , Yang et al, 2014 , Salvati and Beenhakker, 2019 ).…”

Section: Discussionsupporting

confidence: 91%

“…Although the role of HV in typical AS activation has not been clarified ( Bomben et al, 2016 ), experimentally HV-induced alkalosis has been demonstrated to be a trigger of typical AS ( Schuchmann et al, 2009 , Lu et al, 2012 , Salvati and Beenhakker, 2019 ) and humans ( Yang et al, 2014 ). In murine models, alkalosis resulted in up-regulation of VGCCs, N-methyl-D-aspartate (NMDA)-type glutamate receptors as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in cortical pyramidal neurons ( Schuchmann et al, 2009 , Lu et al, 2012 ). Concomitantly, a down-regulation of the same channels in the inhibitory cortical neurons was reported resulting in a generalised cortical hyperexcitability state.…”

Section: Discussionmentioning

confidence: 99%

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Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis

Mattozzi

Cerminara

Sotgiu

et al. 2021

Clinical Neurophysiology Practice

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Highlights We show that typical absence seizures (AS) and hyperventilation-induced high amplitude rhythmic slowing (HIHARS) or HIHARS with Altered Awareness (HIHARSAA) can coexist in the same patient, but never at the same time. We found that alkalosis and dysfunction of the same neural network are involved in both AS and HIHARS. AS and HIHARS should be better recognized to avoid misdiagnosis and overtreatment. AS and HIHARS can coexist in the same patient, but never at the same time.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis

Mattozzi

Cerminara

Sotgiu

et al. 2021

Clinical Neurophysiology Practice

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“…Several studies have addressed the question of how neuronal activity elicits changes in intracellular and extracellular H + concentration, sometimes yielding contrasting results (Caldwell et al, 2013;Chen and Chesler, 2015;Cichy et al, 2015;de Curtis et al, 1998;DeVries, 2001;Lu et al, 2012;Palmer et al, 2003;Zhang et al, 2010;Zhao et al, 2011). We studied the effects of sustained heightened neural activity on the extracellular H + concentration by using in vitro models of epileptic-like network states characterized by synchronized neuronal discharges.…”

Section: Neuronal Hyperactivity Causes Localized Extracellular Acidicmentioning

confidence: 99%

Neuronal hyperactivity causes Na+/H+ exchanger-induced extracellular acidification at active synapses

Chiacchiaretta

Latifi

Bramini

et al. 2017

Journal of Cell Science

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Extracellular pH impacts on neuronal activity, which is in turn an important determinant of extracellular H + concentration. The aim of this study was to describe the spatio-temporal dynamics of extracellular pH at synaptic sites during neuronal hyperexcitability. To address this issue we created ex.E 2 GFP, a membrane-targeted extracellular ratiometric pH indicator that is exquisitely sensitive to acidic shifts. By monitoring ex.E 2 GFP fluorescence in real time in primary cortical neurons, we were able to quantify pH fluctuations during network hyperexcitability induced by convulsant drugs or highfrequency electrical stimulation. Sustained hyperactivity caused a pH decrease that was reversible upon silencing of neuronal activity and located at active synapses. This acidic shift was not attributable to the outflow of synaptic vesicle H + into the cleft nor to the activity of membrane-exposed H + V-ATPase, but rather to the activity of the Na + /H + -exchanger. Our data demonstrate that extracellular synaptic pH shifts take place during epileptic-like activity of neural cultures, emphasizing the strict links existing between synaptic activity and synaptic pH. This evidence may contribute to the understanding of the physio-pathological mechanisms associated with hyperexcitability in the epileptic brain.

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“…Hyperventilation leads to carbon dioxide washout and decreased blood PCO 2 levels (hypocapnia) and the respiratory alkalosis that ensues increases neuronal excitability (Aram & Lodge, 1987;Lu et al, 2012;Woolley et al, 1963) and can even precipitate absence seizures (Miley & Forster, 1977;Salvati & Beenhakker, 2019;Watemberg et al, 2015). Voluntary hyperventilation can lead to a substantial drop in PCO 2 levels.…”

Section: Pro -Epilep Ti C Role Of Hyperventil Ation Induced Hyp Oc mentioning

confidence: 99%

A critical analysis of the purported role of hypoxaemia in the comorbidity of obstructive sleep apnoea and epilepsy

Mishra

Jaseja²,

Goyal

2020

Clin Physio Funct Imaging

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Obstructive sleep apnoea (OSA) is a globally prevalent sleep disorder of significant health concern and confounded with several comorbidities resulting in adverse effect(s) on quality of life in patients afflicted with it. Of particular interest is the enigmatic high comorbidity of OSA with epilepsy, the exact underlying pathophysiology of which remains elusive despite a multitude of research performed in the last four decades. Hypoxaemia, which is an important characteristic feature found in OSA during apnoeic spells, has been implicated in the high comorbidity of OSA with epilepsy, the basis of which rests upon hypoxaemia‐mediated brain damage, subcortical release phenomenon, oxidative stress and neuroinflammatory reactions. However, several studies present contradictory evidences that potentially refute the hypoxaemia‐based mechanism. Additionally, the role of hypercapnia thatgenerally accompanies hypoxaemia during apnoeic spells, cannot be overlooked and is known to be potentially protective against neuronal hyperexcitability. Thus, hypoxaemia theory implicated in the high comorbidity of OSA and epilepsy appears weak and refutable. This brief paper studies and critically analyses the role of hypoxaemia in conjunction with hypercapnia in the underlying pathophysiology of the comorbidity.

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Alkalosis leads to the over-activity of cortical principal neurons

Cited by 10 publications

References 39 publications

Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis

Occurrence of hyperventilation-induced high amplitude rhythmic slowing with altered awareness after successful treatment of typical absence seizures and a network hypothesis

Neuronal hyperactivity causes Na+/H+ exchanger-induced extracellular acidification at active synapses

A critical analysis of the purported role of hypoxaemia in the comorbidity of obstructive sleep apnoea and epilepsy

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