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The Journal of Neuroscience, September 1, 1999, 19(17):7268-7277
Properties of Q-Type Calcium Channels in Neostriatal and Cortical
Neurons are Correlated with  Subunit Expression
Paul G.
Mermelstein2,
Robert C.
Foehring2,
Tatiana
Tkatch1,
Wen-Jie
Song2,
Gytis
Baranauskas1, and
D. James
Surmeier1
1 Department of Physiology/NUIN, Northwestern
University Medical School, Chicago, Illinois 60611, and
2 Department of Anatomy and Neurobiology, College of
Medicine, University of Tennessee, Memphis, Tennessee 38163
In brain neurons, P- and Q-type Ca2+ channels
both appear to include a class A  1 subunit. In spite of this
similarity, these channels differ pharmacologically and biophysically,
particularly in inactivation kinetics. The molecular basis for this
difference is unclear. In heterologous systems, alternative splicing
and ancillary  subunits have been shown to alter biophysical
properties of channels containing a class A 1 subunit. To test the
hypothesis that similar mechanisms are at work in native systems, P-
and Q-type currents were characterized in acutely isolated rat
neostriatal, medium spiny neurons and cortical pyramidal neurons using
whole-cell voltage-clamp techniques. Cells were subsequently aspirated
and subjected to single-cell RT-PCR (scRT-PCR) analysis of calcium channel 1 and (1-4) subunit
expression. In both cortical and neostriatal neurons, P- and Q-type
currents were found in cells expressing class A 1
subunit mRNA. Although P-type currents in cortical and neostriatal
neurons were similar, Q-type currents differed significantly in
inactivation kinetics. Notably, Q-type currents in neostriatal
neurons were similar to P-type currents in inactivation rate. The
variation in Q-type channel biophysics was correlated with subunit
expression. Neostriatal neurons expressed significantly higher levels
of 2a mRNA and lower levels of 1b mRNA
than cortical neurons. These findings are consistent with the
association of 2a and 1b subunits with
slow and fast inactivation, respectively. Analysis of 1A
splice variants in the linker between domains I and II failed to
provide an alternative explanation for the differences in inactivation
rates. These findings are consistent with the hypothesis that the
biophysical properties of Q-type channels are governed by subunit
isoforms and are separable from toxin sensitivity.
Key words:
striatum; cortex; cerebellum; medium spiny neurons; pyramidal neurons; single-cell RT-PCR; voltage clamp; calcium channels; subunits; subunits; patch-clamp
Copyright © 1999 Society for Neuroscience 0270-6474/99/19177268-10$05.00/0
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