Maturation of rat cerebellar Purkinje cells reveals an atypical Ca2+ channel current that is inhibited by ω-agatoxin IVA and the dihydropyridine (-)-(S)-Bay K8644

To determine if the properties of Ca2+ channels in cerebellar Purkinje cells change during postnatal development, we recorded Ca2+ channel currents from Purkinje cells in cerebellar slices of mature ( postnatal days ( P) 40-50) and immature (P13-20) rats. We found that at P40-50, the somatic Ca2+ channel current was inhibited by omega-agatoxin IVA at concentrations selective for P-type Ca2+ channels (similar to 85%; IC50, < 1 nM) and by the dihydropyridine (-)-( S)- Bay K8644 (similar to 70%; IC50, similar to 40 nM). (-)-( S)- Bay K8644 is known to activate L-type Ca2+ channels, but the decrease in current was not secondary to the activation of L-type channels because inhibition by (-)-( S)- Bay K8644 persisted in the presence of the L-type channel blocker ( R, S)-nimodipine. By contrast, at P13-20, the current was inhibited by omega-agatoxin IVA (similar to 86%; IC50,similar to 1 nM) and a minor component was inhibited by ( R, S)-nimodipine (similar to 8%). The dihydropyridine (-)-( S)- Bay K8644 had no clear effect when applied alone, but in the presence of ( R, S)-nimodipine it reduced the current (similar to 40%), suggesting that activation of L-type channels by (-)-( S)- Bay K8644 masks its inhibition of non-L-type channels. Our findings indicate that Purkinje neurons express a previously unrecognized type of Ca2+ channel that is inhibited by agatoxin IVA, like prototypical P-type channels, and by (-)-( S)- Bay K8644, unlike classical P-type or L-type channels. During maturation, there is a decrease in the size of the L-type current and an increase in the size of the atypical Ca2+ channel current. These changes may contribute to the maturation of the electrical properties of Purkinje cells.