Astrocytes selectively enhance N-type calcium current in hippocampal neurons

Astrocytes influence neuronal development, synapse formation, and synaptic transmission, partly through affecting neuronal calcium signals. In order to elucidate the extent to which astrocytes modulate neuronal voltage-gated calcium currents, we performed a whole-cell patch clamp analysis of neurons in astrocyte-deplete and astrocyte-enriched conditions. We demonstrate that hippocampal neurons in an astrocyte-enriched environment show augmentation of voltage-gated calcium current at 1-3 days in vitro. Further study in pairs of adjacent neurons showed that the augmentation in calcium current was dependent on direct contact with the astrocyte. Pharmacological analysis demonstrated the augmentation is selective for the N-type calcium current, although immunochemical labeling of the alpha1(B) subunit of the N-type calcium channel was unchanged. These findings show that astrocytes regulate neuronal voltage-gated calcium currents in a contact-dependent manner. The specificity of the effect for the N-type calcium current at early days in culture has special significance regarding the role of astrocytes in hippocampal synaptogenesis.