Channels 

About: Channels is an academic journal. The journal publishes majorly in the area(s): Ion channel & Voltage-dependent calcium channel. It has an ISSN identifier of 1933-6950. It is also open access. Over the lifetime, 951 publications have been published receiving 15973 citations.

Pannexin channels are not gap junction hemichannels

Abstract: Pannexins, a class of membrane channels, bear significant sequence homology with the invertebrate gap junction proteins, innexins, and more distant similarities in their membrane topologies and pharmacological sensitivities with the gap junction proteins, connexins. However, the functional role for the pannexin oligomers or pannexons, is different from connexin oligomers, the connexons. Many pannexin publications have used the term “hemichannels” to describe pannexin oligomers while others use the term “channels” instead. This has led to confusion within the literature about the function of pannexins that promotes the idea that pannexons serve as gap junction hemichannels and thus, have an assembly and functional state as gap junctional intercellular channels. Here, we present the case that unlike the connexin gap junction intercellular channels, so far, pannexin oligomers have repeatedly been shown to be channels that are functional in single membranes, but not as intercellular channels in appositional m...

Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators.

Abstract: TRPA1 is a member of the transient receptor potential (TRP) cation channel family, and is predominantly expressed in nociceptive neurons of dorsal root ganglia (DRG) and trigeminal ganglia. Activation of TRPA1 by environmental irritants such as mustard oil, allicin and acrolein causes acute pain. However, the endogenous ligands that directly activate TRPA1 remain elusive in inflammation. Here, we show that a variety of inflammatory mediators (15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), nitric oxide (NO), hydrogen peroxide (H(2)O(2)), and proton (H(+))) activate human TRPA1 heterologously expressed in HEK cells. These inflammatory mediators induced robust Ca(2+) influx in a subset of mouse DRG neurons. The TRP channel blocker ruthenium red almost completely inhibited neuronal responses by 15d-PGJ(2) and NO, but partially suppressed responses to H(2)O(2) and H(+). Functional characterization of site-directed cysteine mutants of TRPA1 in combination with labeling experiments using biotinylated 15d-PGJ(2) demonstrated that modifications of cytoplasmic N-terminal cysteines (Cys421 and Cys621) were responsible for the activation of TRPA1 by 15d-PGJ(2). In TRPA1 responses to other cysteine-reactive inflammatory mediators, such as NO and H(2)O(2), the extent of impairment by respective cysteine mutations differed from those in TRPA1 responses to 15d-PGJ(2). Interestingly, the Cys421 mutation critically impaired the TRPA1 response to H(+) as well. Our findings suggest that TRPA1 channels are targeted by an array of inflammatory mediators to elicit inflammatory pain in the nervous system.

Contributions of T-type calcium channel isoforms to neuronal firing

Abstract: Low voltage-activated (LVA) T-type calcium channels play critical roles in the excitability of many cell types and are a focus of research aimed both at understanding the physiological basis of calcium channel-dependent signaling and the underlying pathophysiology associated with hyperexcitability disorders such as epilepsy. These channels play a critical role towards neuronal firing in both conducting calcium ions during action potentials and also in switching neurons between distinct modes of firing. In this review the properties of the CaV3.1, CaV3.2 and CaV3.3 T-type channel isoforms is discussed in relation to their individual contributions to action potentials during burst and tonic firing states as well their roles in switching between firing states.

Gating the mechanical channel Piezo1: a comparison between whole-cell and patch recording.

Abstract: Piezo1 is a eukaryotic cation-selective mechanosensitive ion channel To understand channel function in vivo, we first need to analyze and compare the response in the whole cell and the patch In patches, Piezo1 inactivates and the current is fit well by a 3-state model with a single pressure-dependent rate However, repeated stimulation led to an irreversible loss of inactivation Remarkably, the loss of inactivation did not occur on a channel-by-channel basis but on all channels at the same time Thus, the channels are in common mechanical domain Divalent ions decreased the unitary conductance from ~68 pS to ~37 pS, irrespective of the cation species Mg and Ca did not affect inactivation rates, but Zn caused a 3-fold slowing CytochalasinD (cytoD) does not alter inactivation rates or the transition to the non-inactivating mode but does reduce the steady-state response Whole-cell currents were similar to patch currents but also had significant differences In contrast to the patch, cytoD inhibited the current suggesting that the activating forces were transmitted through the actin cytoskeleton Hypotonic swelling that prestressed the cytoskeleton and the bilayer greatly increased the sensitivity of both control and cytoD cells so there are two pathways to transmit force to the channels In contrast to patch, removing divalent ions decreased the whole-cell current The difference between whole cell and patch properties provide new insights into our understanding of the Piezo1 gating mechanisms and cautions against generalization to in situ behavior

Voltage-gated sodium channels and metastatic disease.

Abstract: Voltage-gated Na+ channels (VGSCs) are macromolecular protein complexes containing a pore-forming α subunit and smaller non-pore-forming β subunits. VGSCs are expressed in metastatic cells from a number of cancers. In these cells, Na+ current carried by α subunits enhances migration, invasion and metastasis in vivo. In contrast, the β subunits mediate cellular adhesion and process extension. The prevailing hypothesis is that VGSCs are upregulated in cancer, in general favoring an invasive/metastatic phenotype, although the mechanisms are still not fully clear. Expression of the Nav1.5 α subunit associates with poor prognosis in clinical breast cancer specimens, suggesting that VGSCs may have utility as prognostic markers for cancer progression. Furthermore, repurposing existing VGSC-blocking therapeutic drugs may provide a new strategy to improve outcomes in patients suffering from metastatic disease, which is the major cause of cancer-related deaths, and for which there is currently no cure.