Neurotransmission in the carotid body and anesthesia

Shirahata, Machiko

doi:10.1007/s005400200047

Cited by 9 publications

(6 citation statements)

References 135 publications

(118 reference statements)

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“…GABA agonists depress the hypoxic ventilatory response in mammals in part by inhibiting the carotid sinus nerve discharge [52,53]. Those studies implicate GABA(A) receptors because the effects of exogenous GABA were prevented by bicuculline, an antagonist of GABA(A) receptors [53].…”

Section: Gaba As An Inhibitory Postsynaptic Neurotransmittermentioning

confidence: 99%

Signal processing at mammalian carotid body chemoreceptors

Nurse

Piskuric

2013

Seminars in Cell & Developmental Biology

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Section: Gaba As An Inhibitory Postsynaptic Neurotransmittermentioning

confidence: 99%

Signal processing at mammalian carotid body chemoreceptors

Nurse

Piskuric

2013

Seminars in Cell & Developmental Biology

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“…midazolam and diazepam), which act as positive allosteric GABA A R modulators, have long been known to depress the hypoxic ventilatory response in cats (Shirahata, 2002; see, however, Pokorski et al 1994), rabbits (Kim et al 2006) and humans (Alexander & Gross, 1988). This effect was associated with an inhibition of CB chemoreceptor discharge in isolated CB–sinus nerve preparations, and could be blocked by GABA A R antagonists (Shirahata, 2002; Kim et al 2006). In the present study, we showed immunofluorescence localization of GABA A R β subunits on sensory nerve terminals apposed to CB chemoreceptor type I cells in situ , and the expression of mRNA for several GABA A R subunits in tissue extracts of the parent petrosal ganglia.…”

Section: Discussionmentioning

confidence: 99%

“…Of particular interest is the observation that benzodiazepines, a clinically important class of ionotropic GABA A receptor agonists, have been reported to depress the hypoxic ventilatory response in part by inhibiting CB chemoreceptor afferent activity. Thus, perfusion of the cat and rabbit CB with low doses of midazolam (and/or diazepam) reduced afferent chemoreceptor responses to hypoxia (Shirahata, 2002; Kim et al 2006), and reversal of the effect by bicuculline confirmed that GABA A receptors were involved (Shirahata, 2002; see also, Alexander & Gross, 1988). These data suggested an inhibitory role of GABA at sensory nerve endings during hypoxic chemotransmission.…”

mentioning

confidence: 81%

“…Sedative doses of benzodiazepines (e.g. midazolam and diazepam), which act as positive allosteric GABA A R modulators, have long been known to depress the hypoxic ventilatory response in cats (Shirahata, 2002;see, however, Pokorski et al 1994), rabbits (Kim et al 2006) and humans (Alexander & Gross, 1988). This effect was associated with an inhibition of CB chemoreceptor discharge in isolated CB-sinus nerve preparations, and could be blocked by GABA A R antagonists (Shirahata, 2002;Kim et al 2006).…”

Section: Physiological Role Of Postsynaptic Gaba a Receptors In Carotmentioning

confidence: 99%

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Postsynaptic action of GABA in modulating sensory transmission in co‐cultures of rat carotid body via GABA_A receptors

Zhang¹,

Clarke²,

Zhong³

et al. 2009

The Journal of Physiology

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GABA is expressed in carotid body (CB) chemoreceptor type I cells and has previously been reported to modulate sensory transmission via presynaptic GABA B receptors. Because low doses of clinically important GABA A receptor (GABA A R) agonists, e.g. benzodiazepines, have been reported to depress afferent CB responses to hypoxia, we investigated the potential contribution of GABA A R in co-cultures of rat type I cells and sensory petrosal neurones (PNs). During gramicidin perforated-patch recordings (to preserve intracellular Cl − ), GABA and/or the GABA A agonist muscimol (50 μm) induced a bicuculline-sensitive membrane depolarization in isolated PNs. GABA-induced whole-cell currents reversed at ∼ −38 mV and had an EC 50 of ∼10 μm (Hill coefficient = ∼1) at −60 mV. During simultaneous PN and type I cell recordings at functional chemosensory units in co-culture, bicuculline reversibly potentiated the PN, but not type I cell, depolarizing response to hypoxia. Application of the CB excitatory neurotransmitter ATP (1 μm) over the soma of functional PN induced a spike discharge that was markedly suppressed during co-application with GABA (2 μm), even though GABA alone was excitatory. RT-PCR analysis detected expression of GABAergic markers including mRNA for α1, α2, β2, γ2S, γ2L and γ3 GABA A R subunits in petrosal ganglia extracts. Also, CB extracts contained mRNAs for GABA biosynthetic markers, i.e. glutamate decarboxylase (GAD) isoforms GAD 67A,E, and GABA transporter isoforms GAT 2,3 and BGT-1. In CB sections, sensory nerve endings apposed to type I cells were immunopositive for the GABA A R β subunit. These data suggest that GABA, released from the CB during hypoxia, inhibits sensory discharge postsynaptically via a shunting mechanism involving GABA A receptors.

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“…Furthermore, we might add another risk Because the discovery of the comprehensive mechanism from the sensing of oxygen to its intracellular fate is one of the major challenges in the field of anesthesiology and may be worth the Nobel Prize (in the phrase of Professor Lindahl at the 49th annual meeting of the Japanese Society of Anesthesiologists held in Fukuona, Japan), I have read with great interest the review in this journal by Shirahata [1]. Focusing in particular on how anesthetic agents, nondepolarizing muscle relaxants, and drugs used in anesthesia affect carotid body excitation by hypoxia, she clearly described the complex pathway of hypoxic signal transduction in the carotid body.…”

mentioning

confidence: 97%

Oxygen sensing in the carotid body: inhibited hypoxic respiratory drive with muscle relaxant

Ishibe

2002

Journal of Anesthesia

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role. Acetylcholine (ACh) is known as a neurotransmitter at the neuromuscular junction, at preganglionic synapses, and at all postganglionic parasympathetic fibers. The role of ACh in respiratory control has been extensively studied, and it is thought to play a role in carotid body chemotransduction. Eriksson and colleagues [6] recently observed that vecuronium-induced partial neuromuscular block [corresponding to a train of four (TOF) ratio of 0.70] inhibits the respiratory response to hypoxia but not to hypercarbia, although resting ventilation is sustained during air breathing. This inhibitory effect on the hypoxic respiratory response has also been observed with other nondepolarizing muscle relaxants, such as atracurium and pancuronium [7]. A possible pathway has been suggested by blocking the nicotinic ACh receptors on type I glomus cells in the rat [8]. In addition, Wyon and colleagues [9] demonstrated that hypoxia-induced phrenic nerve activities were partially blocked by arterial injection of vecuronium near the carotid body in the anesthetized rabbit. However, the importance of cholinergic signal transmission during hypoxia in the carotid body is still controversial. It is well known that ACh is released during moderate hypoxemia [10], but ACh is not the sole neurotransmitter in the carotid body [11]. Furthermore, hypoxic respiratory control is not known to interact with muscle relaxants, and clinical adverse effects have been never reported. These considerations have stimulated further investigations of the interaction of neuromuscular blocking and the inhibition of neurochemical sensitivity with hypoxia in the carotid body.If this inhibitory effect is confirmed in clinical situations and reversed by anticholinesterase (anti-ChE), anesthesiologists might be recommended to administer more anti-ChE (neostigmine, physostigmine, edrophonium etc) than necessary to restore the clinical findings of reversed muscle relaxant, such as head lift and hand grip, to reverse inhibition of the hypoxic respiratory drive. Furthermore, we might add another risk

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Neurotransmission in the carotid body and anesthesia

Cited by 9 publications

References 135 publications

Signal processing at mammalian carotid body chemoreceptors

Signal processing at mammalian carotid body chemoreceptors

Postsynaptic action of GABA in modulating sensory transmission in co‐cultures of rat carotid body via GABA_A receptors

Oxygen sensing in the carotid body: inhibited hypoxic respiratory drive with muscle relaxant

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Neurotransmission in the carotid body and anesthesia

Cited by 9 publications

References 135 publications

Signal processing at mammalian carotid body chemoreceptors

Signal processing at mammalian carotid body chemoreceptors

Postsynaptic action of GABA in modulating sensory transmission in co‐cultures of rat carotid body via GABAA receptors

Oxygen sensing in the carotid body: inhibited hypoxic respiratory drive with muscle relaxant

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Postsynaptic action of GABA in modulating sensory transmission in co‐cultures of rat carotid body via GABA_A receptors