| Summary: | Dystonic mutant dtsz hamsters are a model for paroxysmal dystonia. Handling/stress provoke the dystonic attacks. This phenomenon subsedes with maturation, but can be reinvoked when these animals receive sodium channel blockers such as lamotrigine, suggesting a dysfunction of striatal sodium channels. Voltage-gated fast sodium currents (INa+) were studied in acutely isolated striatal neurons from healthy and dtsz hamsters in whole-cell voltage clamp recordings. The action of lamotrigine was tested on (a) current/voltage relationship, (b) kinetics, and (c) steady-state inactivation and activation. Under control conditions, properties of INa+ were not different between healthy and dtsz neurons. With lamotrigine, however, (a) peak currents were significantly less depressed by the drug in neurons from dtsz hamsters as compared to healthy cells, and (b) the steady-state inactivation curve shift of INa+ was less pronounced in dtsz neurons. The results suggest that in dtsz hamsters, fast sodium currents in striatal neurons are more resistant to blockade. This sodium channel alteration might be causal for a functional imbalance between input and output structures of the basal ganglia under conditions of compromised I+Na.
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