Developmental regulation of voltage-sensitive sodium channels in rat skeletal muscle

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1985

OSTI ID:6985752

Sherman, S J

The developmental regulation of the voltage-sensitive Na/sup +/ channel in rat skeletal muscle was studied in vivo and in vitro. In triceps surae muscle developing in vivo the development of TTX-sensitive Na/sup +/ channel occurred primarily during the first three postnatal weeks as determined by the specific binding of (/sup 3/H)saxitoxin. This development proceeded in two separate phases. The first phase occurs independently of continuing motor neuron innervation and accounts for 60% of the adult density of TTX-sensitive Na/sup +/ channels. The second phase, which begins about day 11, requires innervation. Muscle cells in primary culture were found to have both TTX-sensitive and insensitive Na/sup +/ channels. The development of the TTX-sensitive channel, in vitro, paralleled the initial innervation-independent phase of development observed in vivo. The density of TTX-sensitive Na/sup +/ channels in cultured muscle cells was regulated by electrical activity and cytosolic Ca/sup + +/ levels. Pharmacological blockade of the spontaneous electrical activity present in these cells lead to a nearly 2-fold increase in the surface density of TTX-sensitive channels. The turnover time of the TTX-sensitive Na/sup +/ channel was measured by blocking the incorporation of newly synthesized channels with tunicamycin, an inhibitor of N-linked protein glycosylation. The regulation of channel density by electrical activity, cytosolic Ca/sup + +/levels, and agents affecting cyclic neucleotide levels had no effect on the turnover time of the TTX-sensitive Na/sup +/ channel, indicating that these regulatory agents instead affect the synthesis of the channel.

• Research Organization: Washington Univ., Seattle (USA)
• OSTI ID: 6985752
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
ANIMALS
ANTIGENS
BIOELECTRICITY
CATIONS
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CHARGED PARTICLES
ELECTRICITY
IN VITRO
IN VIVO
IONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANES
MUSCLES
ORGANIC COMPOUNDS
PHARMACOLOGY
PROTEINS
RATS
RODENTS
SODIUM COMPOUNDS
TOXIC MATERIALS
TOXINS
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES