Calcium/calmodulin-dependent serine protein kinase CASK modulates the L-type calcium current.

Nafzger, Sabine Naomi; Rougier, Jean-Sébastien (2017). Calcium/calmodulin-dependent serine protein kinase CASK modulates the L-type calcium current. Cell calcium, 61, pp. 10-21. Elsevier 10.1016/j.ceca.2016.10.001

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AIM 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. METHODS AND RESULTS 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. CONCLUSION This study suggests CASK as a novel regulator of Cav1.2 via a modulation of the voltage-gated calcium channel Cav1.2 open probability.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Ionenkanalkrankheiten
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Ionenkanalkrankheiten

UniBE Contributor:

Nafzger, Sabine Naomi and Rougier, Jean-Sébastien

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0143-4160

Publisher:

Elsevier

Language:

English

Submitter:

Verena de Serra Frazao-Bill

Date Deposited:

19 May 2017 13:59

Last Modified:

19 May 2017 13:59

Publisher DOI:

10.1016/j.ceca.2016.10.001

PubMed ID:

27720444

Uncontrolled Keywords:

CASK; L-Type calcium channel; Open probability; Regulation

BORIS DOI:

10.7892/boris.99321

URI:

https://boris.unibe.ch/id/eprint/99321

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