title: Calcium/calmodulin-dependent serine protein kinase CASK modulates the L-type calcium current.
abstract: The L-type voltage-gated calcium channel Cav1.2 mediates the calcium influx into cells upon membrane depolarization. The list of cardiopathies associated to Cav1.2 dysfunctions highlights the importance of this channel in cardiac physiology. Calcium/calmodulin-dependent serine protein kinase (CASK), expressed in cardiac cells, has been identified as a regulator of Cav2.2 channels in neurons, but no experiments have been performed to investigate its role in Cav1.2 regulation.
  
  
  
  Full length or the distal C-terminal truncated of the pore-forming Cav1.2 channel (Cav1.2α1c), both present in cardiac cells, were expressed in TsA-201 cells. In addition, a shRNA silencer, or scramble as negative control, of CASK was co-transfected in order to silence CASK endogenously expressed. Three days post-transfection, the barium current was increased only for the truncated form without alteration of the steady state activation and inactivation biophysical properties. The calcium current, however, was increased after CASK silencing with both types of Cav1.2α1c subunits suggesting that, in absence of calcium, the distal C-terminal counteracts the CASK effect. Biochemistry experiments did not reveals neither an alteration of Cav1.2 channel protein expression after CASK silencing nor an interaction between Cav1.2α1c subunits and CASK. Nevertheless, after CASK silencing, single calcium channel recordings have shown an increase of the voltage-gated calcium channel Cav1.2 open probability explaining the increase of the whole-cell current.
  
  
  
  This study suggests CASK as a novel regulator of Cav1.2 via a modulation of the voltage-gated calcium channel Cav1.2 open probability.
authors.affiliation: Department of Clinical Research, University of Bern, Bern CH-3008, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Nafzger
authors.affiliation: Department of Clinical Research, University of Bern, Bern CH-3008, Switzerland. Electronic address: Jean-Sebastien.Rougier@dkf.unibe.ch.
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Rougier
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D051528:Guanylate Kinases / Q000378:metabolism*; D006801:Humans
chemical_list: D002147:Calmodulin; C106868:CASK kinases; D051528:Guanylate Kinases; D002118:Calcium
keywords: CASK; L-Type calcium channel; Open probability; Regulation