Expression of sodium channels with different saxitoxin affinity during rat forebrain development.
This work characterizes the development of the saxitoxin (STX)-sensitive Na+ channels from rat whole forebrain between embryonic day 15 (E15) and postnatal day 90 (P90), both with binding studies and with single channel studies. The Na+ channel total mRNA and the individual mRNAs encoding Na+ channels I, II and III were also determined. The total STX binding rose about 40-fold from E15 to reach a plateau at P30 and its temporal course correlated with the expression of Na+ channel total mRNA. Low affinity and high-affinity STX binding sites, predominant in embryonic and postnatal forebrains, respectively, were found. The single channel studies of batrachotoxin-modified channels also revealed two main populations. In E15 only low-affinity channels (KD = 32.7 nM; 200 mM NaCl) and in P30 only high affinity ones (KD = 1.6 nM) were present. At P0 channels with intermediate affinity (KD range 3-34 nM) were observed. The increase in affinity was due to a gradual increase in the STX association rate.
Villegas
R
R
Instituto Internacional de Estudios Avanzados (IDEA), Caracas, Venezuela.
Castillo
C
C
Póo
M E
ME
Schnell
S
S
Piernavieja
C
C
Balbi
D
D
Villegas
G M
GM
D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D015152:Blotting, Northern; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D007700:Kinetics; D008051:Lipid Bilayers; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D011247:Pregnancy; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012530:Saxitoxin / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D001496:Batrachotoxins; D018076:DNA, Complementary; D008051:Lipid Bilayers; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015222:Sodium Channels; D012530:Saxitoxin