China
Africa
Explore chapters and articles related to this topic
Cholesterol Modulation of BK (MaxiK; Slo1) Channels
Published in Qiu-Xing Jiang, New Techniques for Studying Biomembranes, 2020
Alex M. Dopico, Anna N. Bukiya, Kelsey North
BK channels are widely expressed in mammalian tissues. In most tissues, BK channels are heteromeric complexes (Figure 7.1) resulting from the association of four BK channel-forming subunits (α), which are encoded by the KCNMA1 or Slo1 gene (these homo-tetramers are often refer to as slo1 channels) and small, regulatory subunits (β1–β4), which are encoded by KCNMB1-4 genes. Slo1 pre-mRNA undergoes abundant alternative splicing, editing and further regulation by miRNA (Shipston and Tian, 2016). These processes, followed by posttranslational modification of both α (Kyle and Braun, 2014; Shipston and Tian, 2016) and β subunits (Lu et al., 2006; Li and Yan, 2016) primarily determine the BK current phenotype. BK channel γ subunits (i.e., leucine-rich repeat containing, or LRRC proteins) have also been identified, and drastically modify BK currents (Lu et al., 2006; Evanson et al., 2014; Li and Yan, 2016) yet the physiological significance of γ subunits in most tissues remains to be fully established.
Do we need to reconsider the classification of vestibular migraine?
Published in Expert Review of Neurotherapeutics, 2021
Patricia Perez-Carpena, Jose A. Lopez-Escamez
The biomarkers described in the literature include laboratory tests, functional tests, radiological findings, and genetic variants, which coincide with the results obtained in this review. However, most of the findings of this review have focused on distinguishing VM from other conditions such as MD or migraine, rather than defining VM itself. In this regard, and according to the relationship between MD and VM reported in this review, preview studies have recorded this association. In fact, VM has been associated with MD in families and the autosomal dominant inheritance and migraine could explain the complex heritability of MD and migraine [112]. The genetics of VM is still in its infancy. Early studies reported rare variants in FHM genes (CACNA1A, ATP1A2, SCN1A) [113–115]. These mutations should be taken into account with PRRT2, due to its possible common pathophysiology VM and migraine. After a genome-wide screening for loci linked to VM, the fine structure mapping demonstrated that the disease gene was located between loci rs244895 and D5S2073 in chromosome 5q35. However, the sequencing of the candidate genes in this region, including KCNMB1, KCNIP1, ATP6V0E, SLC34A1, GABRP, DRD1, and HRH2 did not identify any mutation [116,117].
Circulating miRs-183-5p, -206-3p and -381-3p may serve as novel biomarkers for 4,4’-methylene diphenyl diisocyanate exposure
Published in Biomarkers, 2019
Chen-Chung Lin, Brandon F. Law, Paul D. Siegel, Justin M. Hettick
The physiological roles that miRs-183-5p, -206-3p, and -381-3p play in association with asthma and MDI exposure are currently unknown and are worthy of subsequent functional studies. For this study, we used pathway enrichment assays to predict the functional roles in association with MDI exposure. Many pathways enriched in potential genes regulated by hsa-miR-183-5p were associated with HIV-related diseases; however, the single most significant pathway identified is the neuronal system. One of the protein targets of hsa-miR-183-5p (Table 2, and Supplemental Table S1) identified in the neuronal system is the potassium calcium-activated channel subfamily M regulatory beta subunit 1 (KCNMB1), which is associated with lung diseases such as COPD and asthma (Seibold et al.2008, Cao et al.2014). In the airway smooth muscle (ASM), the increase of intracellular calcium concentration triggered by muscarinic acetylcholine receptors activation cause ASM contraction, and consequently, an asthma attack. The large conductance, Ca2+ and voltage-dependent K+ (BK) channels decrease intracellular calcium concentration leading to ASM relaxation; therefore, the BK channel proteins become potential treatment targets for COPD and asthma (Pelaia et al.2002). The BK channels are composed of a pore forming α-subunit which is encoded by KCNMA1 and a regulatory β-subunit which is encoded by KCNMB1. Interestingly, hsa-miR-183-5p was elevated and has been shown to downregulate KCNMB1 expression in COPD lung tissues (Cao et al.2014). In our study, we identified that hsa-miR-183-5p was elevated after MDI exposure, and subsequent studies should examine if MDI exposure-related elevation of hsa-miR-183-5p will downregulate KCNMB1 in the lung ASM, leading to accumulation of intracellular calcium, smooth muscle contraction, and subsequent asthmatic symptoms.
Why do platelets express K+ channels?
Published in Platelets, 2021
Joy R Wright, Martyn P. Mahaut-Smith
In addition to the K+ channels discussed above, a quantitative transcriptomic analysis of the human platelet ion channelome suggests that other K+ channels and K+ channel regulatory proteins are expressed and thus may contribute to platelet function [2]. RNA transcripts for KCNK6, a 2-pore channel (other names TWIK-2, potassium channel subfamily K member 6), were detected at 7-fold lower level than Kv1.3 (KCNA3), and have also been reported at the protein level [3,7]. KCNK6 is widely expressed in other cells and tissues and has been reported to contribute to vascular contractility [65]; it has also been identified as one of the triggers for macrophage NLRP3 (Nucleotide-binding oligomerization domain-Like Receptor containing Pyrin domain 3) activation of the inflammasome [66] and located in Lamp-1-positive lysosomes in transfected Madin-Darby canine kidney epithelial cells [67]. The identity of ion channels that reside in platelet lysosome membranes or play a role in platelet lysosomal secretion is poorly understood, and our understanding of molecular mechanisms involved in the platelet inflammatory response is still limited. Further validation and characterization of KCNK6 may enhance our knowledge of platelet activation and responses. Platelet mRNA was also detected for KCNMA1 (KCa1.1), the pore-forming subunit of the large conductance calcium-activated K+ channel and three of its regulatory subunits (KCNMB1,2 and 3). Over-expression of KCNMA1 in human hepatic stellate cells (HSC) resulted in reduced migration, and Rotterlin activation of KCNMA1 channels resulted in the downregulation of TGFB1/SMAD3 and JAK/STAT3 signaling pathways [68]. Meanwhile, a mutation in KCNMA1 that reduced channel conductance and ion selectivity resulted in impaired mitochondrial function [69].