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bioRxiv · 10.1101/702514

Kv2.1 mediates spatial and functional coupling of L-type calcium channels and ryanodine receptors in neurons

Vierra, N. C.·Kirmiz, M.·van der List, D.·Santana, L. F.·Trimmer, J. S.
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Abstract

The voltage-gated K+ channel Kv2.1 serves a major structural role in the soma and proximal dendrites of brain neurons, tethering the plasma membrane (PM) to the endoplasmic reticulum (ER). Although Kv2.1 clustering at neuronal ER-PM junctions (EPJs) is tightly regulated and conserved across species, its function at these sites is unclear. By identifying and evaluating proteins in close spatial proximity to Kv2.1-containing EPJs, we discovered that a significant role of Kv2.1 at EPJs is to promote the clustering and functional coupling of PM L-type Ca2+ channels (LTCCs) to ryanodine receptor (RyR) ER Ca2+ release channels. Kv2.1 clustering also unexpectedly enhanced LTCC opening at polarized membrane potentials. This enabled Kv2.1-LTCC-RyR triads to generate localized Ca2+ release events (i.e., Ca2+ sparks) independently of action potentials. Together, these findings uncover a novel mode of LTCC regulation and establish a unique mechanism whereby Kv2.1-associated EPJs provide a molecular platform for localized somatodendritic Ca2+ signals.

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Vierra, N. C., Kirmiz, M., van der List, D., Santana, L. F., Trimmer, J. S.. 2019-07-13. Kv2.1 mediates spatial and functional coupling of L-type calcium channels and ryanodine receptors in neurons. https://doi.org/10.1101/702514

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