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A modulatory role for protein phosphatase 2B (calcineurin) in the regulation of Ca 2+ entry
Author(s) -
Burley J. Russell,
Sihra Talvinder S.
Publication year - 2000
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2000.00178.x
Subject(s) - calcineurin , phosphatase , transfection , microbiology and biotechnology , depolarization , bapta , intracellular , biophysics , calmodulin , chemistry , dephosphorylation , hek 293 cells , biology , biochemistry , phosphorylation , enzyme , medicine , transplantation , receptor , gene
The Ca 2+ /calmodulin‐dependent protein phosphatase 2B (PP2B) also known as calcineurin (CN) has been implicated in the Ca 2+ ‐dependent inactivation of Ca 2+ channels in several cell types. To study the role of calcineurin in the regulation of Ca 2+ ‐channel activity, phosphatase expression was altered in NG108‐15 cells by transfection of sense and antisense plasmid constructs carrying the catalytic subunit of human PP2Bβ 3 . Relative to mock‐transfected (wild‐type) controls, cells overexpressing calcineurin showed dramatically reduced high‐voltage‐activated Ca 2+ currents which were recoverable by the inclusion of 1 μ m FK506 in the patch pipette. Conversely, in cells with reduced calcineurin expression, high‐voltage‐activated Ca 2+ currents were larger relative to controls. Additionally in these cells, low‐voltage‐activated currents were significantly reduced. Analysis of high‐voltage‐activated Ca 2+ 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‐scale Ca 2+ influx across the cell membrane, Ca 2+ ‐dependent inactivation of high‐voltage‐activated Ca 2+ currents was increased in sense cells, and this increase could be reduced by intracellular application of 1 m m BAPTA or 1 μ m FK506. These data support a role of calcineurin in the negative feedback regulation of Ca 2+ entry through voltage‐operated Ca 2+ channels.