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

Abstract

In brain neurons, P- and Q-type Ca2+ 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 α1 and β (β1-4) subunit expression. In both cortical and neostriatal neurons, P- and Q-type currents were found in cells expressing class A α1 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.