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@ARTICLE{Conrad:851427,
author = {Conrad, Rachel and Stölting, Gabriel and Hendriks, Johnny
and Ruello, Giovanna and Kortzak, Daniel and Jordan, Nadine
and Gensch, Thomas and Hidalgo, Patricia},
title = {{R}apid {T}urnover of the {C}ardiac {L}-{T}ype {C}a{V}1.2
{C}hannel by {E}ndocytic {R}ecycling {R}egulates {I}ts
{C}ell {S}urface {A}vailability},
journal = {iScience},
volume = {7},
issn = {2589-0042},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {FZJ-2018-05074},
pages = {1 - 15},
year = {2018},
abstract = {Calcium entry through CaV1.2 L-type calcium channels
regulates cardiac contractility. Here, we study the impact
of exocytic and post-endocytic trafficking on cell surface
channel abundance in cardiomyocytes. Single-molecule
localization and confocal microscopy reveal an intracellular
CaV1.2 pool tightly associated with microtubules from the
perinuclear region to the cell periphery, and with actin
filaments at the cell cortex. Channels newly inserted into
the plasma membrane become internalized with an average time
constant of 7.5 min and are sorted out to the
Rab11a-recycling compartment. CaV1.2 recycling suffices for
maintaining stable L-type current amplitudes over 20 hr
independent of de novo channel transport along microtubules.
Disruption of the actin cytoskeleton re-routes CaV1.2 from
recycling toward lysosomal degradation. We identify
endocytic recycling as essential for the homeostatic
regulation of voltage-dependent calcium influx into
cardiomyocytes. This mechanism provides the basis for a
dynamic adjustment of the channel's surface availability and
thus, of heart's contraction.},
cin = {ICS-4},
ddc = {050},
cid = {I:(DE-Juel1)ICS-4-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30267672},
UT = {WOS:000449735000001},
doi = {10.1016/j.isci.2018.08.012},
url = {https://juser.fz-juelich.de/record/851427},
}