GABA(A) receptor expression and inhibitory post-synaptic currents in cerebellar Purkinje cells in dystrophin-deficient mdx mice.
1. Duchenne muscular dystrophy (DMD) is the second most common fatal genetic disease and arises as a consequence of an absence or disruption of the protein dystrophin. In addition to wasting of the skeletal musculature, boys with DMD have a significant degree of cognitive impairment. 2. We show here that there is no difference between littermate control and mdx mice (a murine model of DMD) in the overall expression of the GABA(A) receptor a1-subunit, supporting the suggestion that it is the clustering at the synapse that is affected and not the expression of the GABA(A) receptor protein. 3. We report a significant reduction in both the frequency and amplitude of spontaneous inhibitory post-synaptic currents in cerebellar Purkinje cells of mdx mice compared with littermate controls, consistent with the reported reduction in the number and size of GABA(A) receptor clusters immunoreactive for a1- and a2-subunits at the post-synaptic densities. 4. These results may explain some of the behavioural problems and cognitive impairment reported in DMD.
Kueh
S L L
SL
School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Head
S I
SI
Morley
J W
JW
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D004195:Disease Models, Animal; D053444:Inhibitory Postsynaptic Potentials; D007700:Kinetics; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000523:psychology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*
C546241:Gabra1 protein, mouse; D011963:Receptors, GABA-A