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Alexis S Hill, Yehuda Ben-Shahar
Degenerin/Epithelial Sodium Channels (DEG/ENaCs) are a large family of animal-specific non-voltage gated ion channels, with enriched expression in neuronal and epithelial tissues. While neuronal DEG/ENaCs were originally characterized as sensory receptor channels, recent studies indicate that several DEG/ENaC family members are also expressed throughout the central nervous system. Human genome-wide association studies have linked DEG/ENaC-coding genes with several neurologic and psychiatric disorders, including epilepsy and panic disorder...
July 12, 2018: Channels
Hiroki Arima, Hidekazu Tsutsui, Yasushi Okamura
Cation channel of Spermatozoa (CatSper) is one of the voltage-gated ion channels consisting of voltage sensor domains (VSDs) and pore-gate domains. CatSper is exclusively expressed in spermatozoa and indispensable for Ca2+ influx into cytosol. Recently, we have reported that the VSD of ascidian CatSper induces Ca2+ -permeable pathways in heterologous expression systems. However, it is not known whether ion permeability through the VSD of CatSper is conserved in mammals. In the present study, electrophysiology and fluorometry in Xenopus oocytes revealed that Ca2+ -permeable paths are also formed by expressing the VSD of murine CatSper...
July 12, 2018: Channels
Pierre Costé de Bagneaux, Marta Campiglio, Bruno Benedetti, Petronel Tuluc, Bernhard E Flucher
Voltage-dependent calcium channels (CaV ) activate over a wide range of membrane potentials, and the voltage-dependence of activation of specific channel isoforms is exquisitely tuned to their diverse functions in excitable cells. Alternative splicing further adds to the stunning diversity of gating properties. For example, developmentally regulated insertion of an alternatively spliced exon 29 in the fourth voltage-sensing domain (VSD IV) of CaV 1.1 right-shifts voltage-dependence of activation by 30 mV and decreases the current amplitude several-fold...
July 12, 2018: Channels
Rou-Mu Hu, David J Tester, Ryan Li, Tianyu Sun, Blaise Z Peterson, Michael J Ackerman, Jonathan C Makielski, Bi-Hua Tan
INTRODUCTION: Individual mutations in the SCN5A-encoding cardiac sodium channel-α subunit usually cause a single cardiac arrhythmia disorder, some cause mixed biophysical or clinical phenotypes. Here we report an infant, female patient harboring a N406K mutation in SCN5A with a marked and mixed biophysical phenotype and assess pathogenic mechanisms. METHODS AND RESULTS: A patient suffered from recurrent seizures during sleep and torsades de pointes with a QTc of 530 ms...
July 7, 2018: Channels
Nancy Dong, David W K Lee, Hong-Shuo Sun, Zhong-Ping Feng
D2 dopamine receptor-mediated suppression of synaptic transmission from interneurons plays a key role in neurobiological functions across species, ranging from respiration to memory formation. In this study, we investigated the mechanisms of D2 receptor-dependent suppression using soma-soma synapse between respiratory interneuron VD4 and LPeD1 in the mollusk Lymnaea stagnalis (L. stagnalis). We studied the effects of dopamine on voltage-dependent Ca2+ current and synaptic vesicle release from the VD4. We report that dopamine inhibits voltage-dependent Ca2+ current in the VD4 by both voltage-dependent and -independent mechanisms...
January 1, 2018: Channels
Appu K Singh, Luke L McGoldrick, Kei Saotome, Alexander I Sobolevsky
Transient receptor potential (TRP) ion channels are molecular sensors of a large variety of stimuli including temperature, mechanical stress, voltage, small molecules including capsaicin and menthol, and lipids such as phosphatidylinositol 4,5-bisphosphate (PIP2 ). Since the same TRP channels may respond to different physical and chemical stimuli, they can serve as signal integrators. Many TRP channels are calcium permeable and contribute to Ca2+ homeostasis and signaling. Although the TRP channel family was discovered decades ago, only recently have the structures of many of these channels been solved, largely by cryo-electron microscopy (cryo-EM)...
January 1, 2018: Channels
Cini Mathew John, Rayan Khaddaj Mallat, Grace George, Taeyeob Kim, Ramesh C Mishra, Andrew P Braun
Endothelial small and intermediate-conductance, Ca2+ -activated K+ channels (KCa2.3 and KCa3.1, respectively) play an important role in the regulation of vascular function and systemic blood pressure. Growing evidence indicates that they are intimately involved in agonist-evoked vasodilation of small resistance arteries throughout the circulation. Small molecule activators of KCa2.x and 3.1 channels, such as SKA-31, can acutely inhibit myogenic tone in isolated resistance arteries, induce effective vasodilation in intact vascular beds, such as the coronary circulation, and acutely decrease systemic blood pressure in vivo...
January 1, 2018: Channels
Bin Zhang, Bei Liu, Carolyn M Roos, Michael A Thompson, Y S Prakash, Jordan D Miller, Rui-Wei Guo
Store depletion has been shown to induce Ca2+ entry by Na+/Ca+ exchange (NCX) 1 reversal in proliferative vascular smooth muscle cells (VSMCs). The study objective was to investigate the role of transient receptor potential canonical (TRPC) channels in store depletion and NCX1 reversal in proliferative VSMCs. In cultured VSMCs, expressing TRPC1, TRPC4, and TRPC6, the removal of extracellular Na+ was followed by a significant increase of cytosolic Ca2+ concentration that was inhibited by KBR, a selective NCX1 inhibitor...
January 1, 2018: Channels
Sha Yan, Pengfei Huang, Ying Wang, Xiongzhi Zeng, Yiya Zhang
Spider venoms are known to contain various toxins that are used as an effective means to capture their prey or to defend themselves against predators. An investigation of the properties of Ornithoctonus huwena (O.huwena) crude venom found that the venom can block neuromuscular transmission of isolated mouse phrenic nerve-diaphragm and sciatic nerve-sartorius preparations. However, little is known about its electrophysiological effects on cardiac myocytes. In this study, electrophysiological activities of ventricular myocytes were detected by 100 μg/mL venom of O...
January 1, 2018: Channels
Eshcar Meisel, William Tobelaim, Meidan Dvir, Yoni Haitin, Asher Peretz, Bernard Attali
Inactivation is an intrinsic property of numerous voltage-gated K+ (Kv) channels and can occur by N-type or/and C-type mechanisms. N-type inactivation is a fast, voltage independent process, coupled to activation, with each inactivation particle of a tetrameric channel acting independently. In N-type inactivation, a single inactivation particle is necessary and sufficient to occlude the pore. C-type inactivation is a slower process, involving the outermost region of the pore and is mediated by a concerted, highly cooperative interaction between all four subunits...
January 1, 2018: Channels
Trine L Toft-Bertelsen, Brian R Larsen, Nanna MacAulay
Cellular volume changes lead to initiation of cell volume regulatory events, the molecular identity of which remains unresolved. We here discuss experimental challenges associated with investigation of volume regulation during application of large, non-physiological osmotic gradients. The TRPV4 ion channel responds to volume increase irrespectively of the molecular mechanism underlying cell swelling, and is thus considered a sensor of volume changes. Evidence pointing towards the involvement of TRPV4 in subsequent volume regulatory mechanisms is intriguing, yet far from conclusive...
January 1, 2018: Channels
Cesar C Ceballos, Rodrigo F O Pena, Antônio C Roque, Ricardo M Leão
The negative slope conductance created by the persistent sodium current (INaP ) prolongs the decay phase of excitatory postsynaptic potentials (EPSPs). In a recent study, we demonstrated that this effect was due to an increase of the membrane time constant. When the negative slope conductance opposes completely the positive slope conductances of the other currents it creates a zero slope conductance region. In this region the membrane time constant is infinite and the decay phase of the EPSPs is virtually absent...
January 1, 2018: Channels
Michael A Sulak, Monica Ghosh, Pritam Sinharoy, Spencer R Andrei, Derek S Damron
Transient receptor potential cation channel, subfamily A, member 1 (TRPA1), is activated by a broad range of noxious stimuli. Cdk5, a member of the Cdk family, has recently been identified as a modulator of pain signaling pathways. In the current study, we investigated the extent to which Cdk5 modulates TRPA1 activity. Cdk5 inhibition was found to attenuate TRPA1 response to agonist in mouse DRG sensory neurons. Additionally, the presence of active Cdk5 was associated with increased TRPA1 phosphorylation in transfected HEK293 cells that was roscovitine-sensitive and absent in the mouse mutant S449A full-length channel...
January 1, 2018: Channels
Qadeer Aziz, Yiwen Li, Andrew Tinker
No abstract text is available yet for this article.
January 1, 2018: Channels
D M Waldner, N C Giraldo Sierra, S Bonfield, L Nguyen, I S Dimopoulos, Y Sauvé, W K Stell, N T Bech-Hansen
Congenital stationary night blindness 2A (CSNB2A) is an X-linked retinal disorder, characterized by phenotypically variable signs and symptoms of impaired vision. CSNB2A is due to mutations in CACNA1F, which codes for the pore-forming α1F subunit of a L-type voltage-gated calcium channel, Cav 1.4. Mouse models of CSNB2A, used for characterizing the effects of various Cacna1f mutations, have revealed greater severity of defects than in human CSNB2A. Specifically, Cacna1f-knockout mice show an apparent lack of visual function, gradual retinal degeneration, and disruption of photoreceptor synaptic terminals...
January 1, 2018: Channels
Martin Nybo Andersen, Lasse Skibsbye, Arnela Saljic, Martin Zahle Larsen, Hanne Borger Rasmussen, Thomas Jespersen
Over the last years extensive kinase-mediated regulation of a number of voltage-gated potassium (Kv) channels important in cardiac electrophysiology has been reported. This includes regulation of Kv1.5, Kv7.1 and Kv11.1 cell surface expression, where the kinase-mediated regulation appears to center around the ubiquitin ligase Nedd4-2. In the present study we examined whether Kv1.4, constituting the cardiac Ito,s current, is subject to similar regulation. In the epithelial Madin-Darby Canine Kidney (MDCK) cell line, which constitutes a highly reproducible model system for addressing membrane targeting, we find, by confocal microscopy, that Kv1...
January 1, 2018: Channels
Franz Hofmann
No abstract text is available yet for this article.
January 1, 2018: Channels
J Marc Simard, Volodymyr Gerzanich
No abstract text is available yet for this article.
January 1, 2018: Channels
Amr A Mahrous, Sherif M Elbasiouny
The spinal cord contains specialized groups of cells called pattern generators, which are capable of orchestrating rhythmic firing activity in an isolated preparation. Different patterns of activity could be generated in vitro including right-left alternating bursting and bursting in which both sides are synchronized. The cellular and network mechanisms that enable these behaviors are not fully understood. We have recently shown that Ca2+ -activated K+ channels (SK channels) control the initiation and amplitude of synchronized bursting in the spinal cord...
January 1, 2018: Channels
Anusha Singh, Rajgopal Govindarajan
No abstract text is available yet for this article.
January 1, 2018: Channels
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