Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract

Rafiq Huda, Sarah L. Pollema-Mays, Zheng Chang, George F. Alheid, Donald R McCrimmon, Marco Martina*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cellular mechanisms of central pH chemosensitivity remain largely unknown. The nucleus of the solitary tract (NTS) integrates peripheral afferents with central pathways controlling breathing; NTS neurons function as central chemosensors, but only limited information exists concerning the ionic mechanisms involved. Acid-sensing ion channels (ASICs) mediate chemosensitivity in nociceptive terminals, where pH values ∼6.5 are not uncommon in inflammation, but are also abundantly expressed throughout the brain where pH is tightly regulated and their role is less clear. Here we test the hypothesis that ASICs are expressed in NTS neurons and contribute to intrinsic chemosensitivity and control of breathing. In electrophysiological recordings from acute rat NTS slices, ∼40% of NTS neurons responded to physiological acidification (pH 7.0) with a transient depolarization. This response was also present in dissociated neurons suggesting an intrinsic mechanism. In voltage clamp recordings in slices, a pH drop from 7.4 to 7.0 induced ASIC-like inward currents (blocked by 100 μm amiloride) in ∼40% of NTS neurons, while at pH ≤ 6.5 these currents were detected in all neurons tested; RT-PCR revealed expression of ASIC1 and, less abundantly, ASIC2 in the NTS. Anatomical analysis of dye-filled neurons showed that ASIC-dependent chemosensitive cells (cells responding to pH 7.0) cluster dorsally in the NTS. Using in vivo retrograde labelling from the ventral respiratory column, 90% (9/10) of the labelled neurons showed an ASIC-like response to pH 7.0, suggesting that ASIC currents contribute to control of breathing. Accordingly, amiloride injection into the NTS reduced phrenic nerve activity of anaesthetized rats with an elevated arterial.

Original languageEnglish (US)
Pages (from-to)4761-4775
Number of pages15
JournalJournal of Physiology
Volume590
Issue number19
DOIs
StatePublished - Oct 1 2012

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Acid Sensing Ion Channels
Solitary Nucleus
Respiration
Neurons
Amiloride
Phrenic Nerve
Coloring Agents
Inflammation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Physiology

Cite this

Huda, Rafiq ; Pollema-Mays, Sarah L. ; Chang, Zheng ; Alheid, George F. ; McCrimmon, Donald R ; Martina, Marco. / Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract. In: Journal of Physiology. 2012 ; Vol. 590, No. 19. pp. 4761-4775.
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abstract = "Cellular mechanisms of central pH chemosensitivity remain largely unknown. The nucleus of the solitary tract (NTS) integrates peripheral afferents with central pathways controlling breathing; NTS neurons function as central chemosensors, but only limited information exists concerning the ionic mechanisms involved. Acid-sensing ion channels (ASICs) mediate chemosensitivity in nociceptive terminals, where pH values ∼6.5 are not uncommon in inflammation, but are also abundantly expressed throughout the brain where pH is tightly regulated and their role is less clear. Here we test the hypothesis that ASICs are expressed in NTS neurons and contribute to intrinsic chemosensitivity and control of breathing. In electrophysiological recordings from acute rat NTS slices, ∼40{\%} of NTS neurons responded to physiological acidification (pH 7.0) with a transient depolarization. This response was also present in dissociated neurons suggesting an intrinsic mechanism. In voltage clamp recordings in slices, a pH drop from 7.4 to 7.0 induced ASIC-like inward currents (blocked by 100 μm amiloride) in ∼40{\%} of NTS neurons, while at pH ≤ 6.5 these currents were detected in all neurons tested; RT-PCR revealed expression of ASIC1 and, less abundantly, ASIC2 in the NTS. Anatomical analysis of dye-filled neurons showed that ASIC-dependent chemosensitive cells (cells responding to pH 7.0) cluster dorsally in the NTS. Using in vivo retrograde labelling from the ventral respiratory column, 90{\%} (9/10) of the labelled neurons showed an ASIC-like response to pH 7.0, suggesting that ASIC currents contribute to control of breathing. Accordingly, amiloride injection into the NTS reduced phrenic nerve activity of anaesthetized rats with an elevated arterial.",
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Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract. / Huda, Rafiq; Pollema-Mays, Sarah L.; Chang, Zheng; Alheid, George F.; McCrimmon, Donald R; Martina, Marco.

In: Journal of Physiology, Vol. 590, No. 19, 01.10.2012, p. 4761-4775.

Research output: Contribution to journalArticle

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AU - McCrimmon, Donald R

AU - Martina, Marco

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