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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...
March 21, 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...
March 13, 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...
February 16, 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...
February 9, 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 30, 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 8, 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
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
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...
November 23, 2017: Channels
Oleg I Barygin, Margarita S Komarova, Tatyana B Tikhonova, Anastasiia S Korosteleva, Maxim V Nikolaev, Lev G Magazanik, Denis B Tikhonov
Proton-gated channels of the ASIC family are widely distributed in the mammalian brain, and, according to the recent data, participate in synaptic transmission. However, ASIC-mediated currents are small, and special efforts are required to detect them. This prompts the search for endogenous ASIC ligands, which can activate or potentiate these channels. A recent finding of the potentiating action of histamine on recombinant homomeric ASIC1a has directed attention to amine-containing compounds. In the present study, we have analyzed the action of histamine, tyramine, and tryptamine on native and recombinant ASICs...
November 13, 2017: Channels
Franz Hofmann
No abstract text is available yet for this article.
November 2, 2017: Channels
Denis B Tikhonov, Boris S Zhorov
The family of P-loop channels, which play key roles in the cell physiology, is characterized by four membrane re-entering extracellular P-loops that connect eight transmembrane helices of the pore-forming domain. The X-ray and cryo-EM structures of the open- and closed-state channels show conserved state-dependent folding despite the sequences are very diverse. In sodium, calcium, TRPV and two-pore channels, the pore-lining helices contain conserved asparagines and may or may not include π-helix bulges. Comparison of the sequence- and 3D-alignemnts suggests that the asparagines appeared in evolution as insertions that are accommodated in two ways: by π-helix bulges, which preserve most of inter-segment contacts, or by twists of the C-terminal thirds and switch of inter-segment contacts...
November 2, 2017: Channels
J Marc Simard, Volodymyr Gerzanich
No abstract text is available yet for this article.
November 2, 2017: Channels
Yen-Yu Yang, Roger Long, Christine Ferrara, Stephen Gitelman, Michael German, Shi-Bing Yang
The ATP-sensitive potassium channel (KATP) functions as a metabo-electric transducer in regulating insulin secretion from pancreatic β-cells. The pancreatic KATP channel is composed of a pore-forming inwardly-rectifying potassium channel, Kir6.2, and a regulatory subunit, sulphonylurea receptor 1 (SUR1). Loss-of-function mutations in either subunit often lead to the development of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). PHHI is a rare genetic disease and most patients present with immediate onset within the first few days after birth...
October 31, 2017: Channels
Anusha Singh, Rajgopal Govindarajan
No abstract text is available yet for this article.
October 6, 2017: Channels
William S Tobelaim, Meidan Dvir, Guy Lebel, Meng Cui, Tal Buki, Asher Peretz, Milit Marom, Yoni Haitin, Diomedes E Logothetis, Joel A Hirsch, Bernard Attali
In the heart, co-assembly of Kv7.1 with KCNE1 produces the slow IKS potassium current, which repolarizes the cardiac action potential and mutations in human Kv7.1 and KCNE1 genes cause cardiac arrhythmias. The proximal Kv7.1 C-terminus binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2) and recently we revealed the competition of PIP2 with the calcified CaM N-lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor a LQT mutation. Data indicated that PIP2 and Ca(2+)-CaM perform the same function on IKS channel gating to stabilize the channel open state...
October 4, 2017: Channels
Mena Abdelsayed, Colin H Peters, Peter C Ruben
No abstract text is available yet for this article.
October 4, 2017: Channels
Takafumi Kawai, Shoki Tatsumi, Shinji Kihara, Kenji Sakimura, Yasushi Okamura
Voltage-gated proton channels (VSOP/Hv1) reportedly promote reactive oxygen species (ROS) production in several immune cell types. However, we recently reported that primary microglia from VSOP/Hv1-deficient mice show higher ROS production than those from WT mice. Microglia may show a distinct activation status between WT and VSOP/Hv1-deficient cells, leading to a distinct level of ROS production between them. This is unlikely, however, because ROS production in VSOP/Hv1-deficient microglia remained higher than in WT microglia when the cells were exposed to LPS...
September 29, 2017: Channels
Juejin Wang, Guang Li, Dejie Yu, Yuk Peng Wong, Tan Fong Yong, Mui Cheng Liang, Ping Liao, Roger Foo, Uta C Hoppe, Tuck Wah Soong
Recently, we reported that homozygous deletion of alternative exon 33 of CaV1.2 calcium channel in the mouse resulted in ventricular arrhythmias arising from increased CaV1.2Δ33 ICaL current density in the cardiomyocytes. We wondered whether heterozygous deletion of exon 33 might produce cardiac phenotype in a dose-dependent manner, and whether the expression levels of RNA splicing factors known to regulate alternative splicing of exon 33 might change in human heart failure. Unexpectedly, we found that exon 33(+/-) cardiomyocytes showed similar CaV1...
September 26, 2017: Channels
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