Effects of deuterium oxide on the rate and dissociation constants for saxitoxin and tetrodotoxin action. Voltage-clamp studies on frog myelinated nerve
Journal Article
·
· J. Gen. Physiol.; (United States)
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), Journal Name: J. Gen. Physiol.; (United States) Vol. 78:2; ISSN JGPLA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Use-dependent block of the voltage-gated Na+ channel by tetrodotoxin and saxitoxin: Effect of pore mutations that change ionic selectivity
Synthesis and testing of tetrodotoxin and batrachotoxin antagonists. Annual report, 1 February 1986-31 January 1987
Multiple saxitoxin-binding sites in bullfrog muscle: tetrodotoxin-sensitive sodium channels and tetrodotoxin-insensitive sites of unknown function
Journal Article
·
Sun Sep 23 20:00:00 EDT 2012
· Journal of General Physiology
·
OSTI ID:1625212
Synthesis and testing of tetrodotoxin and batrachotoxin antagonists. Annual report, 1 February 1986-31 January 1987
Technical Report
·
Thu Feb 26 23:00:00 EST 1987
·
OSTI ID:6957180
Multiple saxitoxin-binding sites in bullfrog muscle: tetrodotoxin-sensitive sodium channels and tetrodotoxin-insensitive sites of unknown function
Journal Article
·
Sun Jan 31 23:00:00 EST 1988
· Mol. Pharmacol.; (United States)
·
OSTI ID:5446361
Related Subjects
551001 -- Physiological Systems-- Tracer Techniques
560162* -- Radionuclide Effects
Kinetics
& Toxicology-- Animals
Plants
Microorganisms
& Cells
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMPHIBIANS
ANIMALS
ANTIGENS
AQUATIC ORGANISMS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
FROGS
HEAVY WATER
HYDROGEN COMPOUNDS
KINETICS
LIPIDS
LIPOPROTEINS
MATERIALS
MYELIN
NERVES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PROTEINS
REACTION KINETICS
RECEPTORS
TOXIC MATERIALS
TOXINS
VERTEBRATES
WATER
560162* -- Radionuclide Effects
Kinetics
& Toxicology-- Animals
Plants
Microorganisms
& Cells
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMPHIBIANS
ANIMALS
ANTIGENS
AQUATIC ORGANISMS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
FROGS
HEAVY WATER
HYDROGEN COMPOUNDS
KINETICS
LIPIDS
LIPOPROTEINS
MATERIALS
MYELIN
NERVES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PROTEINS
REACTION KINETICS
RECEPTORS
TOXIC MATERIALS
TOXINS
VERTEBRATES
WATER