title: Spontaneous calcium spike activity in embryonic spinal neurons is regulated by developmental expression of the Na+, K+-ATPase beta3 subunit.
abstract: Different types and patterns of spontaneous electrical activity drive many aspects of neuronal differentiation. Neurons in the developing Xenopus spinal cord exhibit calcium spikes, which regulate gene transcription and neurotransmitter specification. The ionic currents necessary for spike production have been described. However, the mechanisms that generate the onset of this activity and the basis of its regulation remain unclear. Although signaling molecules appear to act on plasma membrane receptors to trigger calcium spike activity, other mechanisms for spontaneous calcium spike regulation may exist as well. Here, we analyze the developmental expression of the Na(+), K(+)-ATPase beta3 subunit in Xenopus tropicalis embryos and show that its levels are downregulated at a time during embryonic development that coincides with the onset of prominent calcium spike activity in spinal neurons. Inhibition of an earlier increase in beta3 expression leads to more depolarized resting membrane potentials and results in later reduction of spike activity. This suppression of beta3 levels also reduces expression of the store-operated calcium channel subunit, Orai1. These findings suggest that the Na(+), K(+)-ATPase plays a role in initiating calcium spike activity and regulating calcium homeostasis.
authors.affiliation: Department of Bioengineering and Neurobiology Section, Division of Biological Sciences, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, California 92093-0357, USA. lwchang@ucsd.edu
authors.forename: Linda W
authors.initials: LW
authors.lastname: Chang
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Spitzer
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D017610:Calcium Compounds / Q000378:metabolism; D002478:Cells, Cultured; D002840:Chromates / Q000378:metabolism; D004558:Electric Stimulation; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology; D018709:Statistics, Nonparametric; D014981:Xenopus
chemical_list: D017610:Calcium Compounds; D002840:Chromates; D021122:Protein Subunits; D012333:RNA, Messenger; D011189:Potassium Chloride; D000254:Sodium-Potassium-Exchanging ATPase; C033750:calcium chromate(VI); D002118:Calcium