KV2.1 mediates spatial and functional coupling of l-type calcium channels and ryanodine receptors in mammalian neurons

Nicholas C. Vierra, Michael Kirmiz, Deborah van der List, L. Fernando Santana, James S. Trimmer

Research output: Contribution to journalArticle

Abstract

The voltage-gated K+ channel Kv2.1 serves a major structural role in the soma and proximal dendrites of mammalian brain neurons, tethering the plasma membrane (PM) to endoplasmic reticulum (ER). Although Kv2.1 clustering at neuronal ER-PM junctions (EPJs) is tightly regulated and highly conserved, its function remains 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 in mammalian brain neurons.

Original languageEnglish (US)
Article numbere49953
JournaleLife
Volume8
DOIs
StatePublished - Oct 2019

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Calcium-Sensing Receptors
Ryanodine Receptor Calcium Release Channel
Calcium Channels
Cell membranes
Endoplasmic Reticulum
Neurons
Cluster Analysis
Cell Membrane
Brain
Voltage-Gated Potassium Channels
Carisoprodol
Dendrites
Electric sparks
Membrane Potentials
Action Potentials
Membranes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

KV2.1 mediates spatial and functional coupling of l-type calcium channels and ryanodine receptors in mammalian neurons. / Vierra, Nicholas C.; Kirmiz, Michael; van der List, Deborah; Santana, L. Fernando; Trimmer, James S.

In: eLife, Vol. 8, e49953, 10.2019.

Research output: Contribution to journalArticle

Vierra, Nicholas C. ; Kirmiz, Michael ; van der List, Deborah ; Santana, L. Fernando ; Trimmer, James S. / KV2.1 mediates spatial and functional coupling of l-type calcium channels and ryanodine receptors in mammalian neurons. In: eLife. 2019 ; Vol. 8.
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