Paralysis of innervated cultured human muscle fibers affects enzymes differentially

Andrea Martinuzzi, Valerie Askanas, W. King Engel

Research output: Contribution to journalArticle

Abstract

Increased accumulation of muscle-specific isozyme (MSI) of creatine kinase (CK), lactate dehydrogenase (LDH), glycogen phosphorylase (GP), and phosphoglycerate mutase (PGAM) occurs with development and indicates muscle fiber maturation. The expression of MSIs of those four enzymes is greatly enhanced in innervated-contracting as compared to noninnervated and noncontracting cultured human muscle fibers. We have now studied the effect of contractile activity on developmental accumulation of MSIs in innervated-contracting, innervated-paralyzed (2 μM tetrodotoxin for 30 days), and noninnervated-noncontracting cultured human muscle fibers. Muscle acetylcholinesterase (AChE) and total enzyme activities were also studied under the same conditions. We observed a different dependency on contractile activity between total enzymatic activities of CK, LDH, and AChE, which were substantially reduced after paralysis, and GP and PGAM, which were unchanged. The expression of MSIs of CK, GP, PGAM, and LDH was always significantly increased in innervated as compared to noninnervated fibers. While the expression of MSIs of GP and PGAM was the same in contracting-innervated and paralyzed-innervated muscle fibers, the expression of MSIs of CK and LDH in paralyzed-innervated muscle fibers was very slightly decreased as compared to their contracting-innervated controls. Our studies demonstrate that in human muscle: (1) total enzymatic activities and the expression of MSIs of GP and PGAM are regulated by neuronal effect(s); (2) total enzymatic activities of CK, LDH, and AChE depend mainly on muscle contractile activity; and (3) MSIs of CK and LDH are regulated predominantly by neuronal factors and to a much lesser degree by muscle contractile activity.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalJournal of Neurochemistry
Volume54
Issue number1
Publication statusPublished - 1990

Keywords

  • Innervated cultured human muscle
  • Isozymes
  • Paralysis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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