Age-dependent expression of high-voltage activated calcium currents during cerebellar granule cell development in...

Ca2+ currents play a crucial role during neuronal growth. In this paper we describe the development of Ca2+ currents using whole-cell patch-clamp recordings in granule cells of cerebellar slices obtained from 7- to 24-day-old rats. Granule cells expressed high-voltage-activated (HVA) Ca2+ currents in different proportions. The percentage of cells with a measurable HVA current, and the size of HVA current increased in parallel with granule cell maturation. At less than 14 days HVA currents consisted of a fast- and slow-inactivating component, while at more than 19 days only the slow-inactivating component remained. The fast-inactivating component had faster activation and inactivation kinetics, a more negative threshold for activation, and steeper steady-state inactivation than the slow-inactivating component. Nifedipine (5 microM) partially blocked both components. omega-Conotoxin (5 microM, omega-CgTx) blocked the slow-inactivating component rather selectively. These results indicate that HVA currents change their gating and pharmacological properties during development. Although the mechanism at the molecular level remains speculative, the developmental changes of the HVA current are relevant to the processes of granule cell maturation and excitability.