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

Thesis/Dissertation · Tue Jan 01 00:00:00 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
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
MUSCLES
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TRITIUM COMPOUNDS
UPTAKE
CATIONS
CELL CULTURES
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IN VIVO
PHARMACOLOGY
PROTEINS
RATS
SODIUM COMPOUNDS
TOXINS
ALKALI METAL COMPOUNDS
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550201* - Biochemistry- Tracer Techniques