Defective Acetylcholine Receptor Subunit Switch Precedes Atrophy of Slow-Twitch Skeletal Muscle Fibers Lacking ERK1/2 Kinases in Soleus Muscle

Abstract To test the role of extracellular-signal regulated kinases 1 and 2 (ERK1/2) in slow-twitch, type 1 skeletal muscle fibers, we studied the soleus muscle in mice genetically deficient for myofiber ERK1/2. Young adult mutant soleus was drastically wasted, with highly atrophied type 1 fibers, denervation at most synaptic sites, induction of “fetal” acetylcholine receptor gamma subunit (AChRγ), reduction of “adult” AChRε, and impaired mitochondrial biogenesis and function. In weanlings, fiber morphology and mitochondrial markers were mostly normal, yet AChRγ upregulation and AChRε downregulation were observed. Synaptic sites with fetal AChRs in weanling muscle were ~3% in control and ~40% in mutants, with most of the latter on type 1 fibers. These results suggest that: (1) ERK1/2 are critical for slow-twitch fiber growth; (2) a defective γ/ε-AChR subunit switch, preferentially at synapses on slow fibers, precedes wasting of mutant soleus; (3) denervation is likely to drive this wasting, and (4) the neuromuscular synapse is a primary subcellular target for muscle ERK1/2 function in vivo.

Download Full-text

Erratum: Corrigendum: Defective Acetylcholine Receptor Subunit Switch Precedes Atrophy of Slow-Twitch Skeletal Muscle Fibers Lacking ERK1/2 Kinases in Soleus Muscle

Scientific Reports ◽

10.1038/srep45420 ◽

2017 ◽

Vol 7 (1) ◽

Author(s):

Shuo Wang ◽

Bonnie Seaberg ◽

Ximena Paez-Colasante ◽

Mendell Rimer

Keyword(s):

Skeletal Muscle ◽

Acetylcholine Receptor ◽

Soleus Muscle ◽

Muscle Fibers ◽

Receptor Subunit ◽

Skeletal Muscle Fibers ◽

Slow Twitch

Download Full-text

Na current density at and away from end plates on rat fast- and slow-twitch skeletal muscle fibers

AJP Cell Physiology ◽

10.1152/ajpcell.1992.262.1.c229 ◽

1992 ◽

Vol 262 (1) ◽

pp. C229-C234 ◽

Cited By ~ 67

Author(s):

R. L. Ruff

Keyword(s):

Skeletal Muscle ◽

Current Density ◽

Muscle Fibers ◽

Postsynaptic Membrane ◽

Na Current ◽

End Plate ◽

Skeletal Muscle Fibers ◽

Slow Twitch ◽

Slow Twitch Fibers ◽

Fast Twitch

Na current density and membrane capacitance were studied with the loose patch voltage clamp technique on rat fast- and slow-twitch skeletal muscle fibers at three different regions on the fibers: 1) the end plate border, 2) greater than 200 microns from the end plate (extrajunctional), and 3) on the end plate postsynaptic membrane. Fibers were treated with collagenase to improve visualization of the end plate and to enzymatically remove the nerve terminal. The capacitance of membrane patches was similar on fast- and slow-twitch fibers and patches of membrane on the end plate had twice the capacitance of patches elsewhere. For fast- and slow-twitch fibers, the sizes of the Na current normalized to the area of the patch were as follows: end plate greater than end plate border greater than extrajunctional. For both types of fibers, the amplitudes of the Na current normalized to the capacitance of the membrane patch were as follows: end plate approximately end plate border greater than extrajunctional. At each of the three regions, the Na current densities were larger on fast-twitch fibers and fast-twitch fibers had a larger increase in Na current density at the end plate border compared with extrajunctional membrane.

Download Full-text

Capillaries are Embedded in the Sarcolemma of Murine Slow Twitch Skeletal Muscle Fibers

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.854.1 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Brian Glancy ◽

Li-Yueh Hsu ◽

Lam Dao ◽

Matthew Bakalar ◽

Stephanie French ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Fibers ◽

Skeletal Muscle Fibers ◽

Slow Twitch

Download Full-text

Arpp, a New Homolog of Carp, Is Preferentially Expressed in Type 1 Skeletal Muscle Fibers and Is Markedly Induced by Denervation

Laboratory Investigation ◽

10.1038/labinvest.3780459 ◽

2002 ◽

Vol 82 (5) ◽

pp. 645-655 ◽

Cited By ~ 62

Author(s):

Yoshiyuki Tsukamoto ◽

Takao Senda ◽

Toshiya Nakano ◽

Chisato Nakada ◽

Takehiko Hida ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Fibers ◽

Skeletal Muscle Fibers

Download Full-text

Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers

The Journal of Cell Biology ◽

10.1083/jcb.200103020 ◽

2001 ◽

Vol 155 (1) ◽

pp. 27-40 ◽

Cited By ~ 130

Author(s):

Yewei Liu ◽

Zoltán Cseresnyés ◽

William R. Randall ◽

Martin F. Schneider

Keyword(s):

Skeletal Muscle ◽

Electrical Stimulation ◽

Nuclear Translocation ◽

Fiber Type ◽

Muscle Fibers ◽

Adult Skeletal Muscle ◽

Skeletal Muscle Fibers ◽

Slow Twitch ◽

Nuclear Foci ◽

Fast Twitch

TTranscription factor nuclear factor of activated T cells NFATc (NFATc1, NFAT2) may contribute to slow-twitch skeletal muscle fiber type–specific gene expression. Green fluorescence protein (GFP) or FLAG fusion proteins of either wild-type or constitutively active mutant NFATc [NFATc(S→A)] were expressed in cultured adult mouse skeletal muscle fibers from flexor digitorum brevis (predominantly fast-twitch). Unstimulated fibers expressing NFATc(S→A) exhibited a distinct intranuclear pattern of NFATc foci. In unstimulated fibers expressing NFATc–GFP, fluorescence was localized at the sarcomeric z-lines and absent from nuclei. Electrical stimulation using activity patterns typical of slow-twitch muscle, either continuously at 10 Hz or in 5-s trains at 10 Hz every 50 s, caused cyclosporin A–sensitive appearance of fluorescent foci of NFATc–GFP in all nuclei. Fluorescence of nuclear foci increased during the first hour of stimulation and then remained constant during a second hour of stimulation. Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc–GFP without electrical stimulation. Nuclear translocation of NFATc–GFP did not occur with either continuous 1 Hz stimulation or with the fast-twitch fiber activity pattern of 0.1-s trains at 50 Hz every 50 s. The stimulation pattern–dependent nuclear translocation of NFATc demonstrated here could thus contribute to fast-twitch to slow-twitch fiber type transformation.

Download Full-text