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000851427 1001_ $$0P:(DE-Juel1)161207$$aConrad, Rachel$$b0$$ufzj
000851427 245__ $$aRapid Turnover of the Cardiac L-Type CaV1.2 Channel by Endocytic Recycling Regulates Its Cell Surface Availability
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000851427 520__ $$aCalcium 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.
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000851427 7001_ $$0P:(DE-Juel1)156347$$aStölting, Gabriel$$b1$$ufzj
000851427 7001_ $$0P:(DE-Juel1)141764$$aHendriks, Johnny$$b2
000851427 7001_ $$0P:(DE-HGF)0$$aRuello, Giovanna$$b3
000851427 7001_ $$0P:(DE-Juel1)157846$$aKortzak, Daniel$$b4$$ufzj
000851427 7001_ $$0P:(DE-Juel1)131932$$aJordan, Nadine$$b5$$ufzj
000851427 7001_ $$0P:(DE-Juel1)131924$$aGensch, Thomas$$b6$$ufzj
000851427 7001_ $$0P:(DE-Juel1)151357$$aHidalgo, Patricia$$b7$$eCorresponding author
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