Genetic essential tremor in γ-aminobutyric acid_A receptor α1 subunit knockout mice
J. Clin. Invest. Jason E. Kralic, et al. 115:774 doi:10.1172/JCI23625 [Go to this article.]

Figure 3
GABA_A receptor α1^–/– mice exhibit normal Purkinje cell number and morphology but complete loss of both spontaneous mIPSCs and exogenous GABA inhibition of whole-cell voltage-clamp electrophysiological responses. (A) Calbindin staining of Purkinje cell number and morphology in cerebellum of 8-month-old α1^+/+ and α1^–/– mice. Magnification, ×400. (B) Similar spontaneously active Purkinje cells were found in both α1^+/+ (22 of 29 penetrations) and α1^–/– (28 of 36 penetrations) mice. Mean rate for α1^–/– mice (26.7 ± 3.8) did not differ from that of α1^+/+ mice (32.4 ± 5.5). (C) Spontaneous mIPSCs recorded over a 30-second period from a Purkinje cell mechanically dissociated from an α1^+/+ and α1^–/– mouse. Spontaneous postsynaptic picrotoxin-sensitive currents with amplitude greater than 50 pA and fall-times greater than 4 ms were recorded from 10 of 16 α1^+/+ mice and 0 of 14 α1^–/– mice. (D) Whole-cell voltage-clamp recordings were obtained from mechanically dissociated cerebellar Purkinje cells from α1^+/+ and α1^–/– mice. GABA was applied to the neurons by a U-tube. GABA (3, 30, and 100 μM) gated a concentration-dependent inward current when applied to Purkinje cells from α1^+/+ mice, but no current was gated in α1^–/– Purkinje cells. (E) Mean GABA-gated currents from cerebellar Purkinje cells mechanically isolated from α1^+/+ or α1^–/– mice. There was a statistically reliable concentration-related increase in GABA response in the α1^+/+ mice (*P < 0.001) but no effect of GABA in the α1^–/– mice (P > 0.1) (n = 6–11 neurons per group).