Purkinje cells toxicity

Marrs TC, Allen IV, Colgrave HF et al. (1991). Neurotoxicity of 1 -methoxycycloheptatriene - a Purkinje cell toxicant. Human Exp Toxicol, 10, 93-101. 

Figure 16-8. Section of rat brain and cerebellum zone after exposure to toxic chemicals. Note the damaged Purkinje cells and the loss of dendrites.

For example, modifications outside the Q/j domain, such as phosphorylation of ataxin-1 at a crucial serine residue (Emamian et al., 2003) and SUMOylation of Htt (Steffan et al., 2004) are important determinants of toxicity. Moreover, Boat (brother of ataxin-1) was shown to interact with ataxin-1 at multiple sites, and altered expression of Boat in Purkinje cells may contribute to the neurodegeneration in SCAl (Mizutani et al., 2005). Differences in susceptibility to TG-catalyzed cross-linking among the various mutated Q -containing proteins may also contribute to the selectivity. 

Franchini, A., Marchesini, E., Poletti, R., and Ottaviani, E. 2004a. Acute toxic effect of the algal yessotoxin on Purkinje cells from the cerebellum of Swiss CDl mice. Toxicon 43, 347-352. 

There are not many studies addressing the potential toxicity of ethylmercury in animal models. Exposure of rats to ethylmercury results in patchy damage to the granule cells in the cerebellum while the Purkinje cells are generally spared. 

McClain, R. M. and Becker, B. A. (1972). Effects of organolead compounds on rat embryonic and fetal development Toxicol. Appl. Pharmacol., 21, 265 McClain, R. M. and Becker, B. A. (1975). Teratogenicity, fetal toxicity and placental transfer of lead nitrate in rats. Toxicol. Appl. Pharmacol., 31, 72 McConnell, P. and Berry, M. (1978). The effects of undernutrition on Purkinje cell dendritic growth in the rat. J. Comp. Neurol., Yll 159 McConnell, P. and Berry, M. (1979). The effects of postnatal lead exposure on Purkinje cell dendritic development in the rat. Neuropathol. Appl. Neurobiol., 5, 115... 

It is of some interest that in several cases the cerebellar Purkinje cell emerges as a specific target of either deficiency of a trace element or the effects of a toxin. Abnormalities of dendritic development are found both in thyroid hormone deficiency and in the copper-deficiency of the brciin that arises in Menkes disease. Somewhat similar effects may be induced in the mouse by poisoning with methyl mercuiy and in developmented lead toxicity. 

Digoxin (see p. 158) shortens the refractory period in atrial and ventricular myocardial cells while prolonging the effective refractory period and diminishing conduction velocity in Purkinje fibers. Digoxin is used to control the ventricular response rate in atrial fibrillation and flutter. At toxic concentrations, digoxin causes ectopic ventricular beats that may result in ventricular tachycardia and fibrillation. [Note This arrhythmia is usually treated with lidocaine or phenytoin.]... 

Cardiac glycosides increase the influx of calcium, and decrease the outflow of potassium. Because there is little sequestration of calcium in cardiac cells, intracellular calcium may increase to toxic levels, particularly with high doses of the drug, and may exchange for sodium, via the sodium-calcium exchanger. This results in an overload of intracellular sodium and calcium, which, because of the decreased outflow of potassium, is not counterbalanced. Thus, calcium overload is manifested as an early afterdepolarization of the cardiac action potential, which may result in premature depolarization of Purkinje fibers and the appearance of ventricular arrhythmias, which may result in ventricular tachyarrhythmias and death. 

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