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Role of the sarcoplasmic reticulum in regulating the activity‐dependent expression of the glycogen phosphorylase gene in contractile skeletal muscle cells
Author(s) -
Vali Shireen,
Carlsen Richard,
Pessah Isaac,
Gorin Fredric
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(200011)185:2<184::aid-jcp3>3.0.co;2-t
Subject(s) - medicine , ryanodine receptor , thapsigargin , endocrinology , myogenesis , depolarization , skeletal muscle , dantrolene , chemistry , biology , serca , veratridine , myocyte , endoplasmic reticulum , calcium , microbiology and biotechnology , biochemistry , sodium channel , atpase , enzyme , organic chemistry , sodium
Nerve‐evoked contractile activity in skeletal muscle regulates transcript and protein levels of many metabolic genes in a coordinate fashion, including the muscle isozyme of glycogen phosphorylase (MGP). Cellular signaling mechanisms mediating the activity‐dependent modulation of MGP transcript levels were investigated in a spontaneously contractile rat skeletal muscle cell line (Rmo). Mechanisms regulating MGP mRNA levels in Rmo myotubes were compared with those previously shown to modulate the gene encoding the α subunit of the acetylcholine receptor (αAChR). Reducing the resting membrane potential from −78 to −30 mV, either electrochemically (KCl) or by increasing Na + permeability (veratridine): (1) prevented activation of transverse tubules, (2) impeded calcium release by the sarcoplasmic reticulum (SR), and (3) blocked Rmo contractility. MGP mRNA levels decreased to 30% of control levels and αAChR levels increased to 350% following 24 h of depolarization. Differing mechanisms appear to mediate this voltage‐dependent regulation of MGP and αAChR. Inhibition of SR calcium efflux selectively decreased MGP mRNA levels by 30–50% when using dantrolene, thapsigargin, or a dose of ryanodine shown to inactivate Ca 2+ ‐induced SR Ca 2+ release (CICR). By contrast, blockade of voltage sensors in transverse tubules with nifedipine, a dihydroaminopyridine (DHAP) antagonist, selectively increased αAChR mRNA levels by twofold. These data indicate that the voltage‐dependent regulation of AChR gene expression differs from that modulating the MGP gene. KCl‐induced depolarization and dantrolene both inhibit pulsatile SR Ca 2+ efflux in Rmo myotubes, but by differing mechanisms. Depolarization and dantrolene comparably reduced MGP mRNA levels and decreased MGP transcript stability from a t 1/2 of 24 h to 14.5 and 16 h, respectively. Reduced transcript stability can account for the observed reduction in mRNA levels of MGP in noncontractile Rmo myotubes and could be a significant regulatory mechanism in skeletal muscle that coordinates the activity‐dependent expression of MGP with other glycogenolytic genes. J. Cell. Physiol. 185:184–199, 2000. © 2000 Wiley‐Liss, Inc.