Blocking action of intracellularly injected neuraminidase on central synapses in vivo

Abstract

The effect of neuraminidase on synaptic transmission was studied at cholinergic and noncholinergic contacts in the buccal and cerebral ganglion of Ap]lysia. The amplitudes of monosynaptic unitary postsynaptic potentials generated by intracellular stimulation of identified presynaptic neurones were measured as indication for the efficacy of synaptic transmission. Neuraminidase was either intrasomatically injected into a presynaptic neurone, or the whole ganglion was incubated with the enzyme. Intrasomatic injection of the enzyme resulted in complete failure of synaptic transmission. This effect occurred independently of the transmitter used. The synaptic failure was presynaptic in origin. The biophysical characteristics of an injected neurone, particularly the amplitude and propagation of its action potential, did not appear to be affected by neuraminidase. Synaptic transmission and biophysical membrane properties were unaffected by extracellular neuraminidase. We conclude that the synaptic blockade is due to the enzyme's action inside the presynaptic nerve ending. It seems most likely that neuraminidase cleaves sialic-acid-containing-compounds associated with the nerve terminal surface membrane, probably thus causing failure of transmitter release.

Neuroexcitatory actions of Tamiflu and its carboxylate metabolite

“…Our observations in brain slices show that OCB has clear effects on neuronal excitability. Neuraminidase, the enzyme targeted by OCB, can modulate synaptic function [3] and possibly alter propagation of signals based on the fact that many ion channels are glycosylated [6,16]. Alterations in signal propagation may be responsible for the facilitation of the 2 nd PSs because we observed dissociation between enhanced somatic EPSPs and unchanged dendritic EPSPs during administration of OCB, reflecting a form of neuronal hyperexcitability.…”

Electrophysiological and electron microscopic correlations concerning the effects of neuraminidase on canine heart cells.

“…Even though it is a normal constituent of brain cells (Schengrund and Rosenberg, 1970), components of Clostridium (or Vibrio) toxin such as neuraminidase (Hipp et al, 1980) would be expected to have some deleterious effects. However, the functional consequences of removing the glycocalyx from certain types of heart cells has not been determined.…”