Geographutoxin-sensitive and insensitive sodium currents in mouse skeletal muscle developing in situ

1. The whole-cell voltage-clamp technique was used to examine developmental changes of Na+ current properties in single fibres of mouse flexor digitorum brevis muscles developing in situ from birth to 20 days post-natal. 2. Geographutoxin II (GTX II), a novel polypeptide toxin from the marine snail Conus geographus, distinguished two different types of voltage-sensitive Na+ currents: GTX II-sensitive and GTX II-insensitive currents, which corresponded respectively to currents with high or low TTX sensitivity. 3. Voltage-dependent activation and inactivation of the GTX II-insensitive currents occurred at membrane potentials 10-20 mV more negative than those for the GTX II-sensitive currents. 4. The GTX II-insensitive current in fibres from mice older than 8 days inactivated more slowly than the GTX II-sensitive current. However, in fibres from younger mice, the two currents decayed with similar speed. 5. The mean specific Na+ conductance (gNa) for the total (GTX II-sensitive plus GTX II-insensitive) Na+ channels was 0.22 mS/muF at a Na+ concentration of 5 mM at birth. The total gNa increased 6-fold to 1.32 mS/muF during the first 20 days after birth. 6. The mean specific gNa for the GTX II-insensitive channels was 0.15 mS/muF at birth, remained at approximately the same level for the first 8 days, and then decreased progressively to become undetectable by day 16. 7. In muscle fibres denervated 12 days after birth, the GTX II-insensitive gNa increased over the next 8 days, whereas the total gNa increased less than normal. 8. By contrast, in fibres denervated on day 4, the total gNa increased more than normal in the following 8 days, and the GTX II-insensitive specific gNa increased above the level seen at birth. 9. Half-maximal activation and inactivation potentials of the total and the GTX II-insensitive currents shifted in the negative direction by 9-17 mV in the first 8 days after birth. 10. We conclude that the regulatory effects of innervation on the total gNa are either suppressive or enhancing depending on the stage of development. On the other hand, denervation elicits an increase in GTX II-insensitive Na+ currents at all ages studied.