UC San Diego

Different patterns and types of spontaneous electrical activity drive many aspects of neuronal differentiation. In the developing spinal cord, neurons exhibit calcium spikes, which can 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. While signaling molecules appear to act on plasma membrane receptors to trigger calcium spike activity, an autonomous mechanism for spontaneous calcium spike regulation may exist as well. Here, I show that the [beta]3 subunit of the Na⁺, K⁺-ATPase is developmentally regulated during a distinct period of embryonic development that coincides with the timing of high calcium spike activity in Xenopus tropicalisspinal neurons. Altering temporal expression of [beta]3 with a gene-specific morpholino changes resting membrane potentials and results in suppression of spike activity. Modifying developmental [beta]3 expression also reduces expression of the store-operated channel subunit Orai1, suggesting that the Na⁺, K⁺-ATPase plays a role in initiating calcium spike activity and regulating calcium homeostasis