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To study the role of calcineurin in the regulation of Ca<jats:sup>2+<\/jats:sup>\u2010channel activity, phosphatase expression was altered in NG108\u201015 cells by transfection of sense and antisense plasmid constructs carrying the catalytic subunit of human PP2B\u03b2<jats:sub>3<\/jats:sub>. Relative to mock\u2010transfected (wild\u2010type) controls, cells overexpressing calcineurin showed dramatically reduced high\u2010voltage\u2010activated Ca<jats:sup>2+<\/jats:sup> currents which were recoverable by the inclusion of 1\u2003\u03bc<jats:sc>m<\/jats:sc> FK506 in the patch pipette. Conversely, in cells with reduced calcineurin expression, high\u2010voltage\u2010activated Ca<jats:sup>2+<\/jats:sup> currents were larger relative to controls. Additionally in these cells, low\u2010voltage\u2010activated currents were significantly reduced. Analysis of high\u2010voltage\u2010activated Ca<jats:sup>2+<\/jats:sup> currents revealed that the kinetics of inactivation were significantly accelerated in cells overexpressing calcineurin. Following the delivery of a train of depolarizing pulses in experiments designed to produce large\u2010scale Ca<jats:sup>2+<\/jats:sup> influx across the cell membrane, Ca<jats:sup>2+<\/jats:sup>\u2010dependent inactivation of high\u2010voltage\u2010activated Ca<jats:sup>2+<\/jats:sup> currents was increased in sense cells, and this increase could be reduced by intracellular application of 1\u2003m<jats:sc>m<\/jats:sc> BAPTA or 1\u2003\u03bc<jats:sc>m<\/jats:sc> FK506. These data support a role of calcineurin in the negative feedback regulation of Ca<jats:sup>2+<\/jats:sup> entry through voltage\u2010operated Ca<jats:sup>2+<\/jats:sup> channels.<\/jats:p>","DOI":"10.1046\/j.1460-9568.2000.00178.x","type":"journal-article","created":{"date-parts":[[2003,3,6]],"date-time":"2003-03-06T14:33:29Z","timestamp":1046961209000},"page":"2881-2891","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A modulatory role for protein phosphatase 2B (calcineurin) in the regulation of Ca<sup>2+<\/sup> entry"],"prefix":"10.1111","volume":"12","author":[{"given":"J. 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