Immobilization with atrophy induces de novo expression of neuronal nicotinic α7 acetylcholine receptors in muscle contributing to neurotransmission.

Abstract

BACKGROUND:

Mature acetylcholine receptor (AChR) isoform normally mediates muscle contraction. The hypothesis that α7AChRs up-regulate during immobilization and contribute to neurotransmission was tested pharmacologically using specific blockers to mature (waglerin-1), immature (αA-OIVA), and α7AChRs (methyllycaconitine), and nonspecific muscle AChR antagonist, α-bungarotoxin.

METHODS:

Mice were immobilized; contralateral limbs were controls. Fourteen days later, anesthetized mice were mechanically ventilated. Nerve-stimulated tibialis muscle contractions on both sides were recorded, and blockers enumerated above sequentially administered via jugular vein. Data are mean ± standard error.

RESULTS:

Immobilization (N = 7) induced tibialis muscle atrophy (40.6 ± 2.8 vs. 52.1 ± 2.0 mg; P < 0.01) and decrease of twitch tension (34.8 ± 1.1 vs. 42.9 ± 1.5 g; P < 0.01). Waglerin-1 (0.3 ± 0.05 μg/g) significantly (P = 0.001; N = 9) depressed twitch tension on contralateral (≥97%) versus immobilized side (approximately 45%). Additional waglerin-1 (total dose 1.06 ± 0.12 μg/g or approximately 15.0 × ED50 in normals) could not depress twitch of 80% or greater on immobilized side. Immature AChR blocker, αA-OIVA (17.0 ± 0.25 μg/g) did not change tension bilaterally. Administration of α-bungarotoxin (N = 4) or methyllycaconitine (N = 3) caused 96% or greater suppression of the remaining twitch tension on immobilized side. Methyllycaconitine, administered first (N = 3), caused equipotent inhibition by waglerin-1 on both sides. Protein expression of α7AChRs was significantly (N = 3; P < 0.01) increased on the immobilized side.

CONCLUSIONS:

Ineffectiveness of waglerin-1 suggests that the twitch tension during immobilization is maintained by receptors other than mature AChRs. Because αA-OIVA caused no neuromuscular changes, it can be concluded that immature AChRs contribute minimally to neurotransmission. During immobilization approximately 20% of twitch tension is maintained by up-regulation of α-bungarotoxin- and methyllycaconitine-sensitive α7AChRs.

• Authors: Sangseok Lee, Hong-Seuk Yang, Tomoki Sasakawa, Mohammed A S Khan, Ashok Khatri, Masao Kaneki, J A Jeevendra Martyn
• Journal: Anesthesiology (Anesthesiology) Vol. 120 Issue 1 Pg. 76-85 (Jan 2014) ISSN: 1528-1175 [Electronic] United States
• PMID: 24126263 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bungarotoxins
• Conotoxins
• Crotalid Venoms
• Peptides, Cyclic
• alpha7 Nicotinic Acetylcholine Receptor
• alphaA-conotoxin OIVA
• waglerin

Topics

• Animals
• Atrophy
• Blotting, Western
• Bungarotoxins (pharmacology)
• Conotoxins (pharmacology)
• Crotalid Venoms (pharmacology)
• Immobilization (adverse effects)
• In Vitro Techniques
• Male
• Mice
• Mice, Inbred C57BL
• Muscle Contraction (physiology)
• Muscle, Skeletal (innervation, metabolism, pathology)
• Myography
• Neuromuscular Junction (drug effects)
• Peptides, Cyclic (pharmacology)
• Synaptic Transmission (physiology)
• alpha7 Nicotinic Acetylcholine Receptor (biosynthesis, drug effects)