Effects of deuterium oxide on the rate and dissociation constants for saxitoxin and tetrodotoxin action. Voltage-clamp studies on frog myelinated nerve
The actions of tetrodotoxin (TTX) and saxitoxin (STX) in normal water and in deuterium oxide (D/sub 20/) have been studied in frog myelinated nerve. Substitution of D/sub 20/ for H/sub 20/ in normal Ringer's solution has no effect on the potency of TTX in blocking action potentials but increases the potency of STX by approximately 50%. Under voltage clamp, the steady-state inhibition of sodium currents by 1 nM STX is doubled in D/sub 20/ as a result of a halving of the rate of dissociation of STX from the sodium channel; the rate of block by STX is not measurably changed by D/sub 20/. Neither steady-state inhibition nor the on- or off-rate constants of TTX are changed by D/sub 20/ substitution. The isotopic effects on STX binding are observed less than 10 min after the toxin has been added to D/sub 20/, thus eliminating the possibility that slow-exchange (t 1/2 greater than 10 h) hydrogen-binding sites on STX are involved. The results are consistent with a hypothesis that attributes receptor-toxin stabilization to isotopic changes of hydrogen bonding; this interpretation suggests that hydrogen bonds contribute more to the binding of STX than to that of TTX at the sodium channel.
- OSTI ID:
- 5362338
- Journal Information:
- J. Gen. Physiol.; (United States), Vol. 78:2
- Country of Publication:
- United States
- Language:
- English
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HEAVY WATER
BIOLOGICAL EFFECTS
TOXINS
BIOCHEMICAL REACTION KINETICS
FROGS
MYELIN
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AMPHIBIANS
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ANTIGENS
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HYDROGEN COMPOUNDS
KINETICS
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551001 - Physiological Systems- Tracer Techniques