Altered potassium channel function in the superficial dorsal horn of the spastic mouse.
The spastic mouse has a naturally occurring glycine receptor (GlyR) mutation that disrupts synaptic input in both motor and sensory pathways. Here we use the spastic mouse to examine how this altered inhibitory drive affects neuronal intrinsic membrane properties and signal processing in the superficial dorsal horn (SDH), where GlyRs contribute to pain processing mechanisms. We first used in vitro patch clamp recording in spinal cord slices (L3-L5 segments) to examine intrinsic membrane properties of SDH neurones in spastic and age-matched wildtype controls ( approximately P23). Apart from a modest reduction ( approximately 3 mV) in resting membrane potential (RMP), neurones in spastic mice have membrane and action potential (AP) properties identical to wildtype controls. There was, however, a substantial reorganization of AP discharge properties in neurones from spastic mice, with a significant increase (14%) in the proportion of delayed firing neurones. This was accompanied by a change in the voltage sensitivity of rapid A-currents, a possible mechanism for increased delayed firing. To assess the functional consequences of these changes, we made in vivo patch-clamp recordings from SDH neurones in urethane anaesthetized (2.2 g kg(-1), i.p.) spastic and wildtype mice ( approximately P37), and examined responses to innocuous and noxious mechanical stimulation of the hindpaw. Overall, responses recorded in wildtype and spastic mice were similar; however, in spastic mice a small population of spontaneously active neurones ( approximately 10%) exhibited elevated spontaneous discharge frequency and post-pinch discharge rates. Together, these results are consistent with the altered intrinsic membrane properties of SDH neurones observed in vitro having functional consequences for pain processing mechanisms in the spastic mouse in vivo. We propose that alterations in potassium channel function in the spastic mouse compensate, in part, for reduced glycinergic inhibition and thus maintain normal signal processing in the SDH.
Graham
B A
BA
School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia.
Brichta
A M
AM
Schofield
P R
PR
Callister
R J
RJ
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009128:Muscle Spasticity / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*
D015221:Potassium Channels
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