| First Author | Vierra NC | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 31663850 | Mgi Jnum | J:292591 |
| Mgi Id | MGI:6445135 | Doi | 10.7554/eLife.49953 |
| Citation | Vierra NC, et al. (2019) Kv2.1 mediates spatial and functional coupling of L-type calcium channels and ryanodine receptors in mammalian neurons. Elife 8:e49953 |
| abstractText | 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 Ca(2+) channels (LTCCs) to ryanodine receptor (RyR) ER Ca(2+) release channels. Kv2.1 clustering also unexpectedly enhanced LTCC opening at polarized membrane potentials. This enabled Kv2.1-LTCC-RyR triads to generate localized Ca(2+) release events (i.e., Ca(2+) 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 Ca(2+) signals in mammalian brain neurons. |
