The Effect of Tetanus Toxin on Calcium Accumulation By Synaptosomes Isolated From Mouse Cerebral Cortex
Dyer, Sherry A.
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Since ancient times, tetanus toxin has been identified as a serious threat to mankind. Evidence has accumulated which links the neurotoxic effects of the toxin with interference of the release of neurotransmitters from the axon terminals of inhibitory synapses. Given the importance of calcium in many neurosecretory processes, the effect of tetanus toxin on calcium fluxes in synaptosomes, isolated portions of the pre- and postsynaptic nerve terminals, was investigated. Radiolabeled calcium is rapidly accumulated by synaptosomes; this is not due to binding of the calcium as demonstrated by the fact that the calcium ionophore A23l87 can deplete the accumulated calcium from synaptosome preparations. Calcium accumulation by synaptosomes is shown to have both plasma membrane and mitochondrial components. Tetanus toxin decreases the accumulation of radiolabeled calcium by synaptosomes. Treatments which have been shown to inactivate the toxin's neurotoxic activity in vivo also prevent the tetanus toxin effect on calcium uptake in this in vitro assay. Additional studies have shown that tetanus toxin decreases calcium accumulation by neuroblastoma-glioma hybrid cell preparations, but the toxin did not affect calcium accumulation by mouse fibroblast cell preparations which are not derived from neural tissues. Although tetanus toxin can affect the membrane potential of synaptosomes, there appears to be no simple relationship between this effect on membrane potentials and the toxin's effect on transmembrane calcium fluxes. Another bacterial toxin, cholera toxin, glycoprotein hormones, arid nonapeptide hormones all of which have previously been shown to have structural and functional similarities with tetanus toxin are also seen to decrease radiolabeled calcium accumulation by synaptosome preparations. The implications of these results with respect to the mechanism of tetanus toxin action and the relationship between glycoprotein hormones, nonapeptide hormones, and certain bacterial toxins is discussed.If you are not a current K College student, faculty, or staff member, email firstname.lastname@example.org to request access to this SIP.