Accession Number:

ADA207991

Title:

Functional Consequences of Chemical Modification of the Saxitoxin Binding Site on Neuronal Sodium Channels

Descriptive Note:

Annual rept. 1 Sep 1987-31 Aug 1988

Corporate Author:

MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE

Personal Author(s):

Report Date:

1988-11-06

Pagination or Media Count:

15.0

Abstract:

Sodium channels from rat brain have been studied at the single channel level in planar bilayer membranes and by using Sodium 22 tracer flux and Tritium- STX binding methods. The opening and closing gating of BTX-activated Na channels can be modulated by divalent cations. Neither the STX binding site nor the selectivity filter is involved in the effects of divalents on gating. External divalents preferentially slowed the rate of channel opening whereas internal divalents preferentially slowed the closing rate. This suggests that divalents are capable of alternately interacting with elements of the voltage- sensing machinery of the channel that are alternately exposed to the outside and inside as the channel closes and opens. In cultured neonatal rat brain glial cells astrocytes, high affinity STX binding sites and STX-sensitive Sodium 22 influx are virtually absent until day 8 when the density of STX binding sites and STX blockable flux begin to increase. This spontaneous change can be prematurely initiated by placing the cells in a defined culture medium. One or more medium components may regulate the differential expression of STX-sensitive and STX-insensitive Na channels.

Subject Categories:

  • Biochemistry
  • Toxicology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE