Properties of Q-Type Calcium Channels in Neostriatal and Cortical Neurons are Correlated with β Subunit Expression

In brain neurons, P- and Q-type Ca 2+ channels both appear to include a class A α1 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 β subunits have been shown to alter biophysical properties of channels containing a class A α1 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 α 1 and β (β 1–4 ) subunit expression. In both cortical and neostriatal neurons, P- and Q-type currents were found in cells expressing class A α 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 β subunit expression. Neostriatal neurons expressed significantly higher levels of β 2a mRNA and lower levels of β 1b mRNA than cortical neurons. These findings are consistent with the association of β 2a and β 1b subunits with slow and fast inactivation, respectively. Analysis of α 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 β subunit isoforms and are separable from toxin sensitivity.