Sodium currents in striatal neurons from dystonic dt(sz) hamsters: altered response to lamotrigine.
Dystonic mutant dt(sz) 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 (I(Na(+))) were studied in acutely isolated striatal neurons from healthy and dt(sz) 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 I(Na(+)) were not different between healthy and dt(sz) neurons. With lamotrigine, however, (a) peak currents were significantly less depressed by the drug in neurons from dt(sz) hamsters as compared to healthy cells, and (b) the steady-state inactivation curve shift of I(Na(+)) was less pronounced in dt(sz) neurons. The results suggest that in dt(sz) 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).
Siep
E
E
Institute of Physiology, Department of Neurophysiology, Westfälische Wilhelms-Universität Münster, Germany.
Richter
A
A
Löscher
W
W
Speckmann
E-J
EJ
Köhling
R
R
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology*; D006224:Cricetinae; D020821:Dystonic Disorders / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D000077213:Lamotrigine; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000502:physiology; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D015222:Sodium Channels; D014227:Triazines; D012964:Sodium; D000077213:Lamotrigine