Properties of Q-type calcium channels in neostriatal and cortical neurons are correlated with beta subunit expression

In brain neurons, P- and Q-type Ca2+ channels both appear to include a clas s A alpha 1 subunit. In spite of this similarity, these channels differ pha rmacologically and biophysically, particularly in inactivation kinetics. Th e molecular basis for this difference is unclear. In heterologous systems, alternative splicing and ancillary beta subunits have been shown to alter b iophysical properties of channels containing a class A alpha 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 neostriat al, medium spiny neurons and cortical pyramidal neurons using whole-cell vo ltage-clamp techniques. Cells were subsequently aspirated and subjected to single-cell RT-PCR (scRT-PCR) analysis of calcium channel alpha(1) and beta (beta(1-4)) subunit expression. In both cortical and neostriatal neurons, P- and Q-type currents were found in cells expressing class A alpha 1 subun it 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 curr ents in inactivation rate. The variation in Q-type channel biophysics was c orrelated with beta subunit expression. Neostriatal neurons expressed signi ficantly higher levels of beta(2a) mRNA and lower levels of beta(1b) mRNA t han cortical neurons. These findings are consistent with the association of beta(2a) and beta(1b) subunits with slow and fast inactivation, respective ly. Analysis of alpha(1A) splice variants in the linker between domains I a nd II failed to provide an alternative explanation for the differences in i nactivation rates. These findings are consistent with the hypothesis that t he biophysical properties of Q-type channels are governed by beta subunit i soforms and are separable from toxin sensitivity.