Cholesterol-Independent Effects of Methyl-b- Cyclodextrin on Chemical Synapses
Date
2012-05-20Author
Ormerod, Kiel G.
Rogasevskaia, Tatiana P.+-
Coorseen, Jens R.
Mercier, A. Joffre
Metadata
Show full item recordAbstract
The cholesterol chelating agent, methyl-b-cyclodextrin (MbCD), alters synaptic function in many systems. At crayfish
neuromuscular junctions, MbCD is reported to reduce excitatory junctional potentials (EJPs) by impairing impulse
propagation to synaptic terminals, and to have no postsynaptic effects. We examined the degree to which physiological
effects of MbCD correlate with its ability to reduce cholesterol, and used thermal acclimatization as an alternative method to
modify cholesterol levels. MbCD impaired impulse propagation and decreased EJP amplitude by 40% (P,0.05) in
preparations from crayfish acclimatized to 14uC but not from those acclimatized to 21uC. The reduction in EJP amplitude in
the cold-acclimatized group was associated with a 49% reduction in quantal content (P,0.05). MbCD had no effect on input
resistance in muscle fibers but decreased sensitivity to the neurotransmitter L-glutamate in both warm- and coldacclimatized
groups. This effect was less pronounced and reversible in the warm-acclimatized group (90% reduction in cold,
P,0.05; 50% reduction in warm, P,0.05). MbCD reduced cholesterol in isolated nerve and muscle from cold- and warmacclimatized
groups by comparable amounts (nerve: 29% cold, 25% warm; muscle: 20% cold, 18% warm; P,0.05). This
effect was reversed by cholesterol loading, but only in the warm-acclimatized group. Thus, effects of MbCD on glutamatesensitivity
correlated with its ability to reduce cholesterol, but effects on impulse propagation and resulting EJP amplitude
did not. Our results indicate that MbCD can affect both presynaptic and postsynaptic properties, and that some effects of
MbCD are unrelated to cholesterol chelation.