Vs. Vorobjev et al., Differential modulation of AMPA receptors by cyclothiazide in two types ofstriatal neurons, EUR J NEURO, 12(8), 2000, pp. 2871-2880
The modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMP
A) receptor-mediated currents by cyclothiazide was investigated in acutely
isolated cells from rat striatum with whole-cell patch-clamp recording. Sin
gle-cell reverse transcriptase-polymerase chain reaction (RT-PCR) was used
to identify medium spiny and giant aspiny neurons and to determine their AM
PA receptor subunit composition mostly in separate experiments. After pretr
eatment with cyclothiazide, kainate-induced AMPA responses were more strong
ly potentiated in medium spiny than in giant aspiny neurons; cyclothiazide
induced a ninefold leftward shift in the kainate concentration-response cur
ve for medium spiny neurons (not giant aspiny neurons). The EC(50)s for the
cyclothiazide potentiation did not differ substantially between medium spi
ny neurons and giant aspiny neurons. The recovery of kainate-activated curr
ents from modulation by cyclothiazide was slower for medium spiny neurons t
han for giant aspiny neurons. Medium spiny neurons expressed GluR-A, GluR-B
and GluR-C, but not GluR-D subunits in both flip and flop splice variants.
All giant aspiny neurons expressed GluR-A and GluR-D, exclusively in the f
lop form, half of them also expressed GluR-B and GluR-C. This is in keeping
with slow and fast desensitization kinetics in medium spiny neurons and gi
ant aspiny neurons, respectively, and differences in cyclothiazide modulati
on. The rate of cyclothiazide dissociation from the AMPA receptor, activate
d by glutamate, was similar to 90 times slower in medium spiny neurons than
in giant aspiny neurons. In giant aspiny neurons (not medium spiny neurons
) this rate was strongly dependent on the presence of an agonist; 1 mm glut
amate increased it 30-fold. Thus, two major cell groups in the striatum dis
play distinct AMPA receptor compositions carrying specific properties of gl
utamate responses. Excitatory transmission will thus be differentially affe
cted by cyclothiazide-type compounds.