Trafficking and stability of voltage-gated calcium channels

Abstract

Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and internalization of this important ion channel family.

Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression

“…Regulatory cascades can be divided into short-term responses, like conformational changes due to protein–protein interactions or phosphorylation, and long-term regulatory pathways, such as transcriptional regulation and membrane targeting2. Regarding short-term regulation, the LTCC pore unit shows few VDI components, but it is rather regulated by calcium itself through CDI) and CDF, respectively164142.…”

“…The regulation of calcium fluxes occurs at the level of single channel activity and precise channel sublocalization within the plasma membrane2. In cardiomyocytes, this microdomain-confined calcium influx controls the action potential duration and initiates calcium-induced calcium release and subsequent heart muscle contraction34.…”

“…In non-cardiac cells, endoplasmatic reticulum (ER) retention, lateral diffusion and internalization of LTCCs in cytosolic vesicles represent an important additional regulatory mechanism of calcium cycling220. However, LTCC surface delocalization or internalization in cardiomyocytes is still poorly understood.…”

Altering sphingolipid composition with aging induces contractile dysfunction of gastric smooth muscle viaKCa1.1 upregulation

“…Thus, the alternation in acyl chain length or composition of SLs affects K Ca 1.1 expression on the cell surface, without affecting the single‐channel activity of K Ca 1.1. The expression of membrane proteins, including ion channels in the plasma membrane, is determined by a balance between synthesis/forward trafficking from the endoplasmic reticulum, endocytosis, and recycling/degradation (Conn & Ulloa‐Aguirre, 2010; Simms & Zamponi, 2012). Recent studies demonstrate that various K + channel proteins undergo endocytosis and degradation via PKC activation or by glycosphingolipids.…”

Differential interaction of β2e with phosphoinositides: A comparative study between β2e and MARCKS

“…Although the a1 subunit primarily determines the voltage-sensitivity and pharmacological responses of Ca V channels, as auxiliary subunits, b and a2d subunits also play a pivotal role in regulating Ca V channel activity and promoting their membrane expression. 4 In particular, b subunits have a strong influence on the biophysical property of Ca V channel gating. 5,6 With 4 isotypes, b subunits are usually located in the cytosol and bind to the Ca V channel via the a-interacting domain.…”