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https://www.readbyqxmd.com/read/29136290/the-role-of-ca-2-dependent-k-channels-at-the-rat-corticostriatal-synapses-revealed-by-paired-pulse-stimulation
#1
Angel A Robles G, Ana V Vega, Carolina Gonzalez-Sandoval, Jaime Barral
Potassium channels play an important role in modulating synaptic activity both at presynaptic and postsynaptic levels. We have shown before that presynaptically located KV and KIR channels modulate the strength of corticostriatal synapses in rat brain, but the role of other types of potassium channels at these synapses remains largely unknown. Here we show that calcium-dependent potassium channels BK-type but not SK-type channels are located presynaptically in corticostriatal synapses. We stimulated cortical neurons in rat brain slices and recorded postsynaptic excitatory potentials (EPSP) in medium spiny neurons (MSN) in dorsal neostriatum...
November 14, 2017: Synapse
https://www.readbyqxmd.com/read/29058675/dendritic-small-conductance-calcium-activated-potassium-channels-activated-by-action-potentials-suppress-epsps-and-gate-spike-timing-dependent-synaptic-plasticity
#2
Scott L Jones, Minh-Son To, Greg J Stuart
Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation...
October 23, 2017: ELife
https://www.readbyqxmd.com/read/29055091/functional-interaction-of-junctophilin-2-with-small-conductance-ca-2-activated-potassium-channel-subtype-2-sk2-in-mouse-cardiac-myocytes
#3
Hong K Fan, Tian X Luo, Wei D Zhao, Yong H Mu, Yang Yang, Wen J Guo, Hui Y Tu, Qian Zhang
AIM: Junctophilins (JPs), a protein family of the junctional membrane complex, maintain the close conjunction between cell surface and intracellular membranes in striate muscle cells mediating the cross talk between extracellular Ca(2+) entry and intracellular Ca(2+) release. The small conductance Ca(2+) -activated K(+) channels are activated by the intracellular calcium and play an essential role in the cardiac action potential profile. Molecular mechanisms of regulation of the SK channels are still uncertain...
October 21, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29050967/role-of-k-channels-in-regulating-spontaneous-activity-in-the-muscularis-mucosae-of-guinea-pig-bladder
#4
Ken Lee, Ayu Isogai, Minori Antoh, Shunichi Kajioka, Masatoshi Eto, Hikaru Hashitani
To explore the roles of various K(+) channels in regulating the spontaneous activity of bladder muscularis mucosae (MM) that is considered to play an important role in maintaining mucosal function. Effects of K(+) channel modulators on electrical and contractile activity in the guinea-pig bladder MM were examined using intracellular microelectrode and isometric tension recording. The MM predominately generated bursting spontaneous action potentials (SAPs) and phasic contractions (SPCs) that were blocked by nifedipine (1µM)...
October 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29036189/inhibition-of-cug-binding-protein-1-and-activation-of-caspases-are-critically-involved-in-piperazine-derivative-bk10007s-induced-apoptosis-in-hepatocellular-carcinoma-cells
#5
Ju-Ha Kim, Hee Young Kwon, Dong Hoon Ryu, Min-Ho Nam, Bum Sang Shim, Jin Han Kim, Jae Yeol Lee, Sung-Hoon Kim
Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/29035200/small-conductance-ca-2-activated-k-channels-induce-the-firing-pause-periods-during-the-activation-of-drosophila-nociceptive-neurons
#6
Koun Onodera, Shumpei Baba, Akira Murakami, Tadashi Uemura, Tadao Usui
In Drosophila larvae, Class IV sensory neurons respond to noxious thermal stimuli and provoke heat avoidance behavior. Previously, we showed that the activated neurons displayed characteristic fluctuations of firing rates, which consisted of repetitive high-frequency spike trains and subsequent pause periods, and we proposed that the firing rate fluctuations enhanced the heat avoidance (Terada et al., 2016). Here, we further substantiate this idea by showing that the pause periods and the frequency of fluctuations are regulated by small conductance Ca(2+)-activated K(+) (SK) channels, and the SK knockdown larvae display faster heat avoidance than control larvae...
October 16, 2017: ELife
https://www.readbyqxmd.com/read/29018164/termination-of-vernakalant-resistant-atrial-fibrillation-by-inhibition-of-small-conductance-ca-2-activated-k-channels-in-pigs
#7
Jonas Goldin Diness, Lasse Skibsbye, Rafel Simó-Vicens, Joana Larupa Santos, Pia Lundegaard, Carlotta Citerni, Daniel Rafael Peter Sauter, Sofia Hammami Bomholtz, Jesper Hastrup Svendsen, Søren-Peter Olesen, Ulrik S Sørensen, Thomas Jespersen, Morten Grunnet, Bo Hjorth Bentzen
BACKGROUND: Evidence has emerged that small-conductance Ca(2+)-activated K(+) (SK) channels constitute a new target for treatment of atrial fibrillation (AF). SK channels are predominantly expressed in the atria as compared with the ventricles. Various marketed antiarrhythmic drugs are limited by ventricular adverse effects and efficacy loss as AF progresses. METHODS AND RESULTS: A total of 43 pigs were used for the studies. AF reversion in conscious long-term tachypaced pigs: Pigs were subjected to atrial tachypacing (7 Hz) until they developed sustained AF that could not be reverted by vernakalant 4 mg/kg (18...
October 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28991505/modulation-of-sk-channels-regulates-locomotor-alternating-bursting-activity-in-the-functionally-mature-spinal-cord
#8
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 Ca(2+)-activated K(+) channels (SK channels) control the initiation and amplitude of synchronized bursting in the spinal cord...
October 9, 2017: Channels
https://www.readbyqxmd.com/read/28982705/sk-channels-regulate-resting-properties-and-signaling-reliability-of-a-developing-fast-spiking-neuron
#9
Yihui Zhang, Hai Huang
Reliable and precise signal transmission is essential in circuits of the auditory brainstem to encode timing with submillisecond accuracy. Globular bushy cells reliably and faithfully transfer spike signals to the principal neurons of the medial nucleus of the trapezoid body (MNTB) through the giant glutamatergic synapse, the calyx of Held. Thus, the MNTB works as a relay nucleus that preserves the temporal pattern of firing at high frequency. Using whole-cell patch-clamp recordings, we observed a K(+) conductance mediated by small-conductance calcium-activated potassium (SK) channels in the MNTB neurons from rats of either sex...
November 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28978760/ach-induced-hyperpolarization-and-decreased-resistance-in-mammalian-type-ii-vestibular-hair-cells
#10
Lauren Ashlee Poppi, Hessam Tabatabaee, Hannah Rose Drury, Phillip Jobling, Robert J Callister, Americo A Migliaccio, Paivi M Jordan, Joseph Christopher Holt, Richard D Rabbitt, Rebecca Lim, Alan Martin Brichta
In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) increases background afferent discharge; and 2) decreases afferent sensitivity to rotational stimuli. While the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of alpha9-containing nAChRs ( 9nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates...
October 4, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28947806/premature-contractions-of-the-bladder-are-suppressed-by-interactions-between-trpv4-and-sk3-channels-in-murine-detrusor-pdgfr%C3%AE-cells
#11
Haeyeong Lee, Byoung H Koh, Lauren E Peri, Robert D Corrigan, Hyun-Tai Lee, Nikita E George, Bhupal P Bhetwal, Yeming Xie, Brian A Perrino, Toby C Chai, Kenton M Sanders, Sang Don Koh
During filling, urinary bladder volume increases dramatically with little change in pressure. This is accomplished by suppressing contractions of the detrusor muscle that lines the bladder wall. Mechanisms responsible for regulating detrusor contraction during filling are poorly understood. Here we describe a novel pathway to stabilize detrusor excitability involving platelet-derived growth factor receptor-α positive (PDGFRα(+)) interstitial cells. PDGFRα(+) cells express small conductance Ca(2+)-activated K(+) (SK) and TRPV4 channels...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924052/role-of-the-endothelial-caveolae-microdomain-in-shear-stress-mediated-coronary-vasorelaxation
#12
Tong Lu, Xiao-Li Wang, Qiang Chai, Xiaojing Sun, Gary C Sieck, Zvonimir S Katusic, Hon-Chi Lee
In this study, we determined the role of caveolae and the ionic mechanisms that mediate shear stress-mediated vasodilation (SSD). We found that both TRPV4 and SK channels are targeted to caveolae in freshly isolated bovine coronary endothelial cells (BCECs) and that TRPV4 and KCa2.3 (SK3) channels are co-immunoprecipitated by anti-caveolin-1 antibodies. Acute exposure of BCECs seeded in a capillary tube to 10 dynes/cm2 of SS resulted in activation of TRPV4 and SK currents. However, after incubation with HC067047 (TRPV4 inhibitor) SK currents could no longer be activated by SS, suggesting SK channel activation by SS was mediated through TRPV4...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28902181/platelet-derived-growth-factor-receptor-alpha-positive-cells-a-new-cell-type-in-the-human-ureteropelvic-junction
#13
Manuela Hunziker, Anne-Marie O'Donnell, Prem Puri
BACKGROUND: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis. Normal ureteral motility requires coordinated interaction between neurons, smooth muscle cells (SMCs), and interstitial Cajal-like cells (IC-LCs). Recently, a new type of interstitial cell, platelet-derived growth factor receptor α-positive (PDGFRα(+)) cells, was discovered in the gastrointestinal tract and bladder.MethodsWe used immunohistochemistry to study PDGFRα protein distribution in normal human UPJ and congenital UPJ obstruction...
December 2017: Pediatric Research
https://www.readbyqxmd.com/read/28886082/haloperidol-induces-pharmacoepigenetic-response-by-modulating-mirna-expression-global-dna-methylation-and-expression-profiles-of-methylation-maintenance-genes-and-genes-involved-in-neurotransmission-in-neuronal-cells
#14
Babu Swathy, Moinak Banerjee
INTRODUCTION: Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. METHODS: SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28884460/potassium-channels-a-potential-therapeutic-target-for-parkinson-s-disease
#15
REVIEW
Xiaoyan Chen, Bao Xue, Jun Wang, Haixia Liu, Limin Shi, Junxia Xie
The pathogenesis of the second major neurodegenerative disorder, Parkinson's disease (PD), is closely associated with the dysfunction of potassium (K(+)) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K(+) channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K(+) channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum...
September 7, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28878623/mechanisms-of-spontaneous-climbing-fiber-discharge-evoked-pauses-and-output-modulation-of-cerebellar-purkinje-cell-in-mice
#16
Xian-Hua Jin, Hong-Wei Wang, Xin-Yuan Zhang, Chun-Ping Chu, Yuan-Zhe Jin, Song-Biao Cui, De-Lai Qiu
Climbing fiber (CF) afferents modulate the frequency and patterns of cerebellar Purkinje cell (PC) simple spike (SS) activity, but its mechanism is unclear. In the present study, we investigated the mechanisms of spontaneous CF discharge-evoked pauses and the output modulation of cerebellar PCs in urethane-anesthetized mice using in vivo whole-cell recording techniques and pharmacological methods. Under voltage-clamp recording conditions, spontaneous CF discharge evoked strong inward currents followed by small conductance calcium-activated potassium (SK) channels that mediated outward currents...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28858616/inferior-olivary-tmem16b-mediates-cerebellar-motor-learning
#17
Yang Zhang, Zhushan Zhang, Shaohua Xiao, Jason Tien, Son Le, Trieu Le, Lily Y Jan, Huanghe Yang
Ca(2+)-activated ion channels shape membrane excitability and Ca(2+) dynamics in response to cytoplasmic Ca(2+) elevation. Compared to the Ca(2+)-activated K(+) channels, known as BK and SK channels, the physiological importance of Ca(2+)-activated Cl(-) channels (CaCCs) in neurons has been largely overlooked. Here we report that CaCCs coexist with BK and SK channels in inferior olivary (IO) neurons that send climbing fibers to innervate cerebellar Purkinje cells for the control of motor learning and timing...
August 30, 2017: Neuron
https://www.readbyqxmd.com/read/28818302/mitochondrial-ca-2-activated-k-channels-and-their-role-in-cell-life-and-death-pathways
#18
REVIEW
Inge E Krabbendam, Birgit Honrath, Carsten Culmsee, Amalia M Dolga
Ca(2+)-activated K(+) channels (KCa) are expressed at the plasma membrane and in cellular organelles. Expression of all KCa channel subtypes (BK, IK and SK) has been detected at the inner mitochondrial membrane of several cell types. Primary functions of these mitochondrial KCa channels include the regulation of mitochondrial ROS production, maintenance of the mitochondrial membrane potential and preservation of mitochondrial calcium homeostasis. These channels are therefore thought to contribute to cellular protection against oxidative stress through mitochondrial mechanisms of preconditioning...
July 22, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28790888/amyloid-%C3%AE-1-42-a%C3%AE-1-42-induces-the-cdk2-mediated-phosphorylation-of-tau-through-the-activation-of-the-mtorc1-signaling-pathway-while-promoting-neuronal-cell-death
#19
Ki Hoon Lee, Sei-Jung Lee, Hyun Jik Lee, Gee Euhn Choi, Young Hyun Jung, Dah Ihm Kim, Amr Ahmed Gabr, Jung Min Ryu, Ho Jae Han
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment and memory loss. Amyloid β1-42 (Aβ) and hyper-phosphorylation of microtubule-associated protein tau have been considered as major histological features in AD. However, the mechanism of how Aβ induces the hyper-phosphorylation of tau remains to be clarified. In the present study, we investigated the underlying cellular mechanisms of Aβ with regard to the cell cycle regulatory protein-mediated phosphorylation of tau in promoting neuronal cell death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28738160/atrial-selective-k-channel-blockers-potential-antiarrhythmic-drugs-in-atrial-fibrillation
#20
Ursula Ravens
In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K(+)) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles...
November 2017: Canadian Journal of Physiology and Pharmacology
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