Down regulation of sodium channels in nerve terminals of spontaneously epileptic mice.
Tottering mice, in which a single gene lesion leads to prolonged hyperexcitability and spontaneous epilepsy, were studied to determine whether enhanced electrical activity leads to down regulation of sodium channels in central neurons. The number of sodium channels in synaptosomes, as assessed by saxitoxin binding, was decreased from 5.38 +/- 0.06 pmol/mg protein in coisogenic controls to 3.85 +/- 0.10 pmol/mg protein (P less than 0.001) in tottering mice without a change in the KD for saxitoxin. Neurotoxin-activated 22Na+ influx per sodium channel was increased 80% in tottering mice (P less than 0.001). Evidently, the increased level of electrical excitability characteristic of the tottering phenotype causes down regulation of the sodium-channel number and alteration of channel function in the nerve terminals of central neurons.
D029845:Amphibian Proteins; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D004827:Epilepsy / Q000503:physiopathology*; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008818:Mice, Neurologic Mutants; D009411:Nerve Endings / Q000502:physiology*; D012530:Saxitoxin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism / Q000502:physiology*
D029845:Amphibian Proteins; D002352:Carrier Proteins; D007473:Ion Channels; C027525:saxitoxin-binding protein, Rana catesbeiana; D012530:Saxitoxin; D012964:Sodium