Dystonia is a neurological disorder characterized by an excessive co-contraction of agonist and antagonist muscles. It has been suggested that malfunction of the basal ganglia is the unique origin of this disease. However, symptoms from different types of dystonia have shown that dysfunction of the cerebellum may contribute to this disease as well. One type of dystonia that shows cerebellar symptoms is called Rapid-onset dystonia-parkinsonism (RDP). Interestingly, this genetic disease manifests a specific mutation that reduces the function of the Na/K ATPase pump α3 isoform which is the exclusive isoform expressed in Purkinje cells. A reduction of the current generated by the electrogenic Na/K ATPase may affect the regulation of the spontaneous activity of Purkinje cells and therefore the generation of precise timing signals that allow motor coordination. We propose that disruption of this activity may be the mechanism by which the cerebellum induces dystonia. Purkinje cells are the main cells of the cerebellar cortex and it is thought that the information required for motor coordination is encoded in their activity. In order to understand the role of Purkinje cells in motor coordination, it is important to learn how synaptic inputs and the conductances responsible for intrinsic firing affect the rate and pattern of activity of these cells. Although the contribution of ionic channels in regulation of spontaneous firing has been studied, little is known about the effect of the electrogenic Na/K-ATPase pump on it. Considering that the sodium load provided every action potential by the activation of voltage-dependent sodium channels makes a significant contribution to the Na/K ATPase pump current and that Purkinje cells fire at high frequencies, a high activity of the sodium pump in these cells is expected. Therefore, we examined whether the outward current generated by the activity of the pump is significant enough to contribute to regulation of membrane excitability. Additionally, we determined whether the amplitude of the pump current would proportionally scale with increases of the firing rate and if this effect acts as a negative feedback mechanism to regulate the rate of spontaneous activity. We found that spontaneous activity of Purkinje cells is exquisitely sensitive to dysfunction of sodium pumps. Furthermore, preliminary data supports the notion that the outward current of the sodium pump acts as a negative feedback mechanism to regulate the rate of spontaneous activity.
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