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However, there has been little evidence suggesting Ca<jats:sup>2+<\/jats:sup>signals from extracellular sources are influenced by PS1. Here we report that the Ca<jats:sup>2+<\/jats:sup>currents carried by voltage-dependent Ca<jats:sup>2+<\/jats:sup>channels are increased in PS1-deficient cortical neurons. This increase is mediated by a significant increase in the contributions of L- and P-type Ca<jats:sup>2+<\/jats:sup>channels to the total voltage-mediated Ca<jats:sup>2+<\/jats:sup>conductance in PS1 (\u2212\/\u2212) neurons. In addition, chelating intracellular Ca<jats:sup>2+<\/jats:sup>with 1,2-bis-( o-aminophenoxy)ethane- N,N,N\u2032,N\u2032-tetraacetic acid (BAPTA) produced an increase in Ca<jats:sup>2+<\/jats:sup>current amplitude that was comparable to the increase caused by PS1 deficiency. In contrast to this, BAPTA had no effect on voltage-dependent Ca<jats:sup>2+<\/jats:sup>conductances in PS1-deficient neurons. These data suggest that PS1 deficiency may influence voltage-gated Ca<jats:sup>2+<\/jats:sup>channel function by means that involve intracellular Ca<jats:sup>2+<\/jats:sup>signaling. These findings reveal that PS1 functions at multiple levels to regulate and stabilize intracellular Ca<jats:sup>2+<\/jats:sup>levels that ultimately control neuronal firing behavior and influence synaptic transmission.<\/jats:p>","DOI":"10.1152\/jn.00745.2005","type":"journal-article","created":{"date-parts":[[2005,9,8]],"date-time":"2005-09-08T00:33:37Z","timestamp":1126139617000},"page":"4421-4429","source":"Crossref","is-referenced-by-count":11,"title":["Presenilin 1 Deficiency Alters the Activity of Voltage-Gated Ca<sup>2+<\/sup>Channels in Cultured Cortical Neurons"],"prefix":"10.1152","volume":"94","author":[{"given":"David G.","family":"Cook","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheree 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