Cholesterol-independent effects of methyl-?-cyclodextrin on chemical synapses.

ABSTRACT: The cholesterol chelating agent, methyl-?-cyclodextrin (M?CD), alters synaptic function in many systems. At crayfish neuromuscular junctions, M?CD 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 M?CD correlate with its ability to reduce cholesterol, and used thermal acclimatization as an alternative method to modify cholesterol levels. M?CD impaired impulse propagation and decreased EJP amplitude by 40% (P<0.05) in preparations from crayfish acclimatized to 14 °C but not from those acclimatized to 21 °C. The reduction in EJP amplitude in the cold-acclimatized group was associated with a 49% reduction in quantal content (P<0.05). M?CD had no effect on input resistance in muscle fibers but decreased sensitivity to the neurotransmitter L-glutamate in both warm- and cold-acclimatized 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). M?CD reduced cholesterol in isolated nerve and muscle from cold- and warm-acclimatized 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 M?CD on glutamate-sensitivity correlated with its ability to reduce cholesterol, but effects on impulse propagation and resulting EJP amplitude did not. Our results indicate that M?CD can affect both presynaptic and postsynaptic properties, and that some effects of M?CD are unrelated to cholesterol chelation.

SUBMITTER: Ormerod KG 

PROVIDER: S-EPMC3348160 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature