title: L-Type calcium channels mediate calcium oscillations in early postnatal Purkinje neurons.
abstract: Ca(2+) signaling is important in many fundamental neuronal processes including neurotransmission, synaptic plasticity, neuronal development, and gene expression. In cerebellar Purkinje neurons, Ca(2+) signaling has been studied primarily in the dendritic region where increases in local Ca(2+) have been shown to occur with both synaptic events and spontaneous electrical activity involving P-type voltage-gated Ca(2+) channels (VGCCs), the predominant VGCC expressed by Purkinje neurons. Here we show that Ca(2+) signaling is also a prominent feature of immature Purkinje neurons at developmental stages that precede expression of dendritic structure and involves L-type rather than P-type VGCCs. Immature Purkinje neurons acutely dissociated from postnatal day 4-7 rat pups exhibit spontaneous cytoplasmic Ca(2+) oscillations. The Ca(2+) oscillations require entry of extracellular Ca(2+), are blocked by tetrodotoxin, are communicated to the nucleus, and correlate closely with patterns of endogenously generated spontaneous and evoked electrical activity recorded in the neurons. Immunocytochemistry showed that L-, N-, and P/Q-types of VGCCs are present on the somata of the Purkinje neurons at this age. However, only the L-type VGCC antagonist nimodipine effectively antagonized the Ca(2+) oscillations; inhibitors of P/Q and N-type VGCCs were relatively ineffective. Release of Ca(2+) from intracellular Ca(2+) stores significantly amplified the Ca(2+) signals of external origin. These results show that a somatic signaling pathway that generates intracellular Ca(2+) oscillations and involves L-type VGCCs and intracellular Ca(2+) stores plays a prominent role in the Ca(2+) dynamics of early developing Purkinje neurons and may play an important role in communicating developmental cues to the nucleus.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: P
authors.initials: P
authors.lastname: Liljelund
authors.forename: J G
authors.initials: JG
authors.lastname: Netzeband
authors.forename: D L
authors.initials: DL
authors.lastname: Gruol
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D026941:Sodium Channel Blockers; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D005904:Glial Fibrillary Acidic Protein; D026941:Sodium Channel Blockers; D005680:gamma-Aminobutyric Acid; D002118:Calcium