The Potassium Channel Odyssey: Mechanisms of Traffic and Membrane Arrangement

Abstract

Ion channels are transmembrane proteins that conduct specific ions across biological membranes. Ion channels are present at the onset of many cellular processes, and their malfunction triggers severe pathologies. Potassium channels (KChs) share a highly conserved signature that is necessary to conduct K+ through the pore region. To be functional, KChs require an exquisite regulation of their subcellular location and abundance. A wide repertoire of signatures facilitates the proper targeting of the channel, fine-tuning the balance that determines traffic and location. These signature motifs can be part of the secondary or tertiary structure of the protein and are spread throughout the entire sequence. Furthermore, the association of the pore-forming subunits with different ancillary proteins forms functional complexes. These partners can modulate traffic and activity by adding their own signatures as well as by exposing or masking the existing ones. Post-translational modifications (PTMs) add a further dimension to traffic regulation. Therefore, the fate of a KCh is not fully dependent on a gene sequence but on the balance of many other factors regulating traffic. In this review, we assemble recent evidence contributing to our understanding of the spatial expression of KChs in mammalian cells. We compile specific signatures, PTMs, and associations that govern the destination of a functional channel.

Mimicking Cellular Signaling Pathways within Synthetic Multicompartment Vesicles with Triggered Enzyme Activity and Induced Ion Channel Recruitment

“…The control of cellular signaling pathways includes changes in protein activity, protein concentration, protein–protein interactions, and protein localization . With respect to the latter, triggered recruitment of cellular receptors, transporters, and ion channels from internal compartments (early endosomes or recycling endosomes) to the cell membrane and vice versa is important to control and fine‐tune cellular signaling, as has been described for neurons and cardiac muscle cells …”

“…On the contrary, when the subcompartments are non‐responsive or the external stimulus is not present, the multicompartment stays intact. The combination of a primary signal (presence of stimulus in the environment of multicompartments) with a secondary one (induced ion flow to/from the environment) represents a straightforward model that can be used to study ion channel recruitment from internal subcompartments to the membrane upon cellular signaling, a process naturally occurring in neuronal cells . Triggered activity and change in the architecture of synthetic multicompartment vesicles, in auto‐controlled sequences, are expected to open new directions for applications of such functional systems in domains such as medicine, catalysis, and biosensing.…”

Nuclear localization of calcium-activated BK channels in skate ampullary electroreceptors

“…Trafficking of potassium channels to intracellular organelles or plasma membranes is subject to complex regulation that includes alternative splicing to incorporate specific addresses, posttranslational modifications such as phosphorylation or glycosylation and association with accessory subunits [30,31]. The voltage-gated K channel, Kv10.1 is linked to diverse cancers [32].…”

A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens

“…The opening of these channels induces K + efflux, hyperpolarization of cells, and decreases cellular excitability [14][15][16]. K + channels are divided into subgroups based on their molecular structures and mechanisms of activation [17,18]. These subgroups include (i) voltage-gated (Kv), (ii) inward rectifier (Kir), (iii) ion (calcium/sodium)-activated (KCa/Na), and (iv) two-pore (K2p) K + channels.…”

“…We also predicted that METHpre-injected animals would show greater incubation of METH-seeking behaviors than rats pre-injected with saline before METH SA. Because K + channels are key functional players in the regulation of diverse cellular functions including neurotransmitter release and neuronal excitability [17,46,47], we thought it likely that saline-and METH-pretreated animals would show differences in the expression of these channels, with rats pre-exposed to METH showing lower expression of K + channels than the saline-pretreated animals and the controls based on the results of our previous study on the expression of potassium channels in METH SA rats [5]. We also sought to determine if changes in gene expression correlated with altered DNA methylation after METH SA.…”