An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses

Rebecca Mongeon, Michael Walogorsky, Jason Urban, Gail Mandel, Fumihito Ono, Paul Brehm

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Fast and slow skeletal muscle types in larval zebrafish can be distinguished by a fivefold difference in the time course of their synaptic decay. Single-channel recordings indicate that this difference is conferred through kinetically distinct nicotinic acetylcholine receptor (AChR) isoforms. The underlying basis for this distinction was explored by cloning zebrafish muscle AChR subunit cDNAs and expressing them in Xenopus laevis oocytes. Measurements of single-channel conductance and mean open burst duration assigned α2βδε to fast muscle synaptic current. Contrary to expectations, receptors composed of only αβδ subunits (presumed to be α2βδ2 receptors) recapitulated the kinetics and conductance of slow muscle single-channel currents. Additional evidence in support of γ/ε-less receptors as mediators of slow muscle synapses was reflected in the inward current rectification of heterologously expressed α2βδ2 receptors, a property normally associated with neuronal-type nicotinic receptors. Similar rectification was reflected in both single-channel and synaptic currents in slow muscle, distinguishing them from fast muscle. The final evidence for α2βγ2 receptors in slow muscle was provided by our ability to convert fast muscle synaptic currents to those of slow muscle by knocking down ε subunit expression in vivo. Thus, for the first time, muscle synaptic function can be ascribed to a receptor isoform that is composed of only three different subunits. The unique functional features offered by the α2βγ2 receptor likely play a central role in mediating the persistent contractions characteristic to this muscle type.

Original languageEnglish (US)
Pages (from-to)353-366
Number of pages14
JournalJournal of General Physiology
Volume138
Issue number3
DOIs
StatePublished - Sep 2011

Fingerprint

Cholinergic Receptors
Zebrafish
Synapses
Muscles
Nicotinic Receptors
Protein Isoforms
Xenopus laevis
Oocytes
Organism Cloning
Skeletal Muscle
Complementary DNA

ASJC Scopus subject areas

  • Physiology

Cite this

An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses. / Mongeon, Rebecca; Walogorsky, Michael; Urban, Jason; Mandel, Gail; Ono, Fumihito; Brehm, Paul.

In: Journal of General Physiology, Vol. 138, No. 3, 09.2011, p. 353-366.

Research output: Contribution to journalArticle

Mongeon, Rebecca ; Walogorsky, Michael ; Urban, Jason ; Mandel, Gail ; Ono, Fumihito ; Brehm, Paul. / An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses. In: Journal of General Physiology. 2011 ; Vol. 138, No. 3. pp. 353-366.
@article{0d1c69c418d9411a9592de31f82ed34a,
title = "An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses",
abstract = "Fast and slow skeletal muscle types in larval zebrafish can be distinguished by a fivefold difference in the time course of their synaptic decay. Single-channel recordings indicate that this difference is conferred through kinetically distinct nicotinic acetylcholine receptor (AChR) isoforms. The underlying basis for this distinction was explored by cloning zebrafish muscle AChR subunit cDNAs and expressing them in Xenopus laevis oocytes. Measurements of single-channel conductance and mean open burst duration assigned α2βδε to fast muscle synaptic current. Contrary to expectations, receptors composed of only αβδ subunits (presumed to be α2βδ2 receptors) recapitulated the kinetics and conductance of slow muscle single-channel currents. Additional evidence in support of γ/ε-less receptors as mediators of slow muscle synapses was reflected in the inward current rectification of heterologously expressed α2βδ2 receptors, a property normally associated with neuronal-type nicotinic receptors. Similar rectification was reflected in both single-channel and synaptic currents in slow muscle, distinguishing them from fast muscle. The final evidence for α2βγ2 receptors in slow muscle was provided by our ability to convert fast muscle synaptic currents to those of slow muscle by knocking down ε subunit expression in vivo. Thus, for the first time, muscle synaptic function can be ascribed to a receptor isoform that is composed of only three different subunits. The unique functional features offered by the α2βγ2 receptor likely play a central role in mediating the persistent contractions characteristic to this muscle type.",
author = "Rebecca Mongeon and Michael Walogorsky and Jason Urban and Gail Mandel and Fumihito Ono and Paul Brehm",
year = "2011",
month = "9",
doi = "10.1085/jgp.201110649",
language = "English (US)",
volume = "138",
pages = "353--366",
journal = "Journal of General Physiology",
issn = "0022-1295",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses

AU - Mongeon, Rebecca

AU - Walogorsky, Michael

AU - Urban, Jason

AU - Mandel, Gail

AU - Ono, Fumihito

AU - Brehm, Paul

PY - 2011/9

Y1 - 2011/9

N2 - Fast and slow skeletal muscle types in larval zebrafish can be distinguished by a fivefold difference in the time course of their synaptic decay. Single-channel recordings indicate that this difference is conferred through kinetically distinct nicotinic acetylcholine receptor (AChR) isoforms. The underlying basis for this distinction was explored by cloning zebrafish muscle AChR subunit cDNAs and expressing them in Xenopus laevis oocytes. Measurements of single-channel conductance and mean open burst duration assigned α2βδε to fast muscle synaptic current. Contrary to expectations, receptors composed of only αβδ subunits (presumed to be α2βδ2 receptors) recapitulated the kinetics and conductance of slow muscle single-channel currents. Additional evidence in support of γ/ε-less receptors as mediators of slow muscle synapses was reflected in the inward current rectification of heterologously expressed α2βδ2 receptors, a property normally associated with neuronal-type nicotinic receptors. Similar rectification was reflected in both single-channel and synaptic currents in slow muscle, distinguishing them from fast muscle. The final evidence for α2βγ2 receptors in slow muscle was provided by our ability to convert fast muscle synaptic currents to those of slow muscle by knocking down ε subunit expression in vivo. Thus, for the first time, muscle synaptic function can be ascribed to a receptor isoform that is composed of only three different subunits. The unique functional features offered by the α2βγ2 receptor likely play a central role in mediating the persistent contractions characteristic to this muscle type.

AB - Fast and slow skeletal muscle types in larval zebrafish can be distinguished by a fivefold difference in the time course of their synaptic decay. Single-channel recordings indicate that this difference is conferred through kinetically distinct nicotinic acetylcholine receptor (AChR) isoforms. The underlying basis for this distinction was explored by cloning zebrafish muscle AChR subunit cDNAs and expressing them in Xenopus laevis oocytes. Measurements of single-channel conductance and mean open burst duration assigned α2βδε to fast muscle synaptic current. Contrary to expectations, receptors composed of only αβδ subunits (presumed to be α2βδ2 receptors) recapitulated the kinetics and conductance of slow muscle single-channel currents. Additional evidence in support of γ/ε-less receptors as mediators of slow muscle synapses was reflected in the inward current rectification of heterologously expressed α2βδ2 receptors, a property normally associated with neuronal-type nicotinic receptors. Similar rectification was reflected in both single-channel and synaptic currents in slow muscle, distinguishing them from fast muscle. The final evidence for α2βγ2 receptors in slow muscle was provided by our ability to convert fast muscle synaptic currents to those of slow muscle by knocking down ε subunit expression in vivo. Thus, for the first time, muscle synaptic function can be ascribed to a receptor isoform that is composed of only three different subunits. The unique functional features offered by the α2βγ2 receptor likely play a central role in mediating the persistent contractions characteristic to this muscle type.

UR - http://www.scopus.com/inward/record.url?scp=80054002555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054002555&partnerID=8YFLogxK

U2 - 10.1085/jgp.201110649

DO - 10.1085/jgp.201110649

M3 - Article

C2 - 21844221

AN - SCOPUS:80054002555

VL - 138

SP - 353

EP - 366

JO - Journal of General Physiology

JF - Journal of General Physiology

SN - 0022-1295

IS - 3

ER -