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SK channels

Xiao-Dong Zhang, Zana A Coulibaly, Wei Chun Chen, Hannah A Ledford, Jeong Han Lee, Padmini Sirish, Gu Dai, Zhong Jian, Frank Chuang, Ingrid Brust-Mascher, Ebenezer N Yamoah, Ye Chen-Izu, Leighton T Izu, Nipavan Chiamvimonvat
Small-conductance Ca2+ -activated K+ (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca2+ microdomains necessary for SK channel activation. SK currents coupled with Ca2+ influx via L-type Ca2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca2+ store, suggesting that LTCCs provide the immediate Ca2+ microdomain for the activation of SK channels in cardiomyocytes...
March 16, 2018: Scientific Reports
Lie Wang, Giri Kumar Chandaka, Robert C Foehring, Joseph C Callaway, William E Armstrong
Oxytocin (OT) neurons exhibit larger afterhyperpolarizations (AHPs) following spike trains during pregnancy and lactation, when these neurons burst and release more OT. Calcium-dependent AHPs mediated by SK channels show this plasticity, and are reduced when the channel is phosphorylated by casein kinase 2 (CK2), and increased when dephosphorylated by protein phosphatase 2A (PP2A), by altering Ca2+ sensitivity. We compared AHP currents in supraoptic OT neurons after CK2 inhibition with 4,5,6,7-tetrabromobenzotriazole (TBB), or PP1-PP2A inhibition with okadaic acid (OA) focusing on the peak current at 100 ms representing the SK-mediated, medium AHP (ImAHP )...
March 14, 2018: Journal of Neurophysiology
Lina A Matschke, Susanne Rinné, Terrance P Snutch, Wolfgang H Oertel, Amalia M Dolga, Niels Decher
The physiological, intrinsic activity of noradrenergic locus coeruleus (LC) neurons is important for the control of sleep/wakefulness, cognition and autonomous body functions. Dysregulations of the LC-noradrenergic network contribute to the pathogenesis of psychiatric disorders and are key findings in early stages of neurodegenerative diseases. Therefore, identifying ion channels mediating the intrinsic pacemaking mechanism of LC neurons, which is in turn directly coupled to Ca2+ homeostasis and cell survival signaling pathways, can help to foster our understanding of the vulnerability of these neurons in neurodegenerative diseases...
March 7, 2018: Molecular and Cellular Neurosciences
Mohammad Tariqul Islam, Sk Tanvir Ahmed, Ishmam Zabir, Celia Shahnaz, Shaikh Anowarul Fattah
Photoplethysmographic (PPG) signal is getting popularity for monitoring heart rate in wearable devices because of simplicity of construction and low cost of the sensor. The task becomes very difficult due to the presence of various motion artefacts. In this study, an algorithm based on cascade and parallel combination (CPC) of adaptive filters is proposed in order to reduce the effect of motion artefacts. First, preliminary noise reduction is performed by averaging two channel PPG signals. Next in order to reduce the effect of motion artefacts, a cascaded filter structure consisting of three cascaded adaptive filter blocks is developed where three-channel accelerometer signals are used as references to motion artefacts...
February 2018: Healthcare Technology Letters
Mingshuai Wang, Nianzeng Xing, Liyang Wu, Wen-Chu Huang, Zhenqun Xu, Guiming Liu
Enhanced spontaneous contractions are associated with overactive bladder. Elevated levels of reactive oxygen species might contribute to enhanced spontaneous contractions. We investigated the regulation of spontaneous contractions and the effects of hydrogen peroxide (H2 O2 ) in intact rat bladder strips. The spontaneous contractions were measured using a tissue bath system. The vehicle or the specific activators/blockers were applied and followed by the application of 0.003 g% H2 O2 . The basal tension, amplitude, and frequency of spontaneous contractions were quantified...
2018: BioMed Research International
Michael E Authement, Ludovic D Langlois, Ryan D Shepard, Caroline A Browne, Irwin Lucki, Haifa Kassis, Fereshteh S Nugent
Centrally released corticotropin-releasing factor or hormone (extrahypothalamic CRF or CRH) in the brain is involved in the behavioral and emotional responses to stress. The lateral habenula (LHb) is an epithalamic brain region involved in value-based decision-making and stress evasion. Through its inhibition of dopamine-mediated reward circuitry, the increased activity of the LHb is associated with addiction, depression, schizophrenia, and behavioral disorders. We found that extrahypothalamic CRF neurotransmission increased neuronal excitability in the LHb...
March 6, 2018: Science Signaling
Kunsala T D S Yapa, Jennifer Deuis, Amelia A Peters, Paraic A Kenny, Sarah J Roberts-Thomson, Irina Vetter, Gregory R Monteith
AIMS: To assess levels of the calcium permeable transient receptor potential cation channel, subfamily melastatin, member 8 (TRPM8) in breast cancer molecular subtypes and to assess the consequences of TRPM8 pharmacological inhibition with AMTB (an inhibitor of TRPM8) on breast cancer cell lines. MATERIALS AND METHODS: Cell viability and migration of breast cancer cells was determined using MTS assays and wound healing assays, respectively. RNA-Seq analysis of breast tumours and qPCR in breast cancer cell lines were used to assess mRNA levels of ion channels...
February 26, 2018: Life Sciences
Beryl Y T Chung, Craig D C Bailey
The hippocampal formation forms a cognitive circuit that is critical for learning and memory. Cholinergic input to nicotinic acetylcholine receptors plays an important role in the normal development of principal neurons within the hippocampal formation. However, the ability of nicotinic receptors to stimulate principal neurons across all regions of the developing hippocampal formation has not been determined. We show here that heteromeric nicotinic receptors mediate direct inward current and depolarization responses in principal neurons across the hippocampal formation of the young postnatal mouse...
January 31, 2018: Journal of Neurophysiology
Yuhong Liu, Victoria Cole, Isabella Lawandy, Afshin Ehsan, Frank W Sellke, Jun Feng
We have recently found that diabetes is associated with the inactivation of the calcium-activated potassium channels (KCa) in endothelial cells, which may contribute to endothelial dysfunction in diabetic patients at baseline. In the current study, we further investigated the effects of diabetes on coronary arteriolar responses to the small (SK) and intermediate (IK) KCa opener NS309 in diabetic and non-diabetic patients and correlated that data with the changes in the SK/IK protein expression/distribution in the setting of cardioplegic ischemia and reperfusion (CP) and cardiopulmonary bypass (CPB)...
January 5, 2018: Molecular and Cellular Biochemistry
Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang
Small-conductance Ca2+ -activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin...
December 7, 2017: Scientific Reports
Xiaorong Xu Parks, Donatella Contini, Paivi M Jordan, Joseph C Holt
In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs) synapse on type II hair cells, bouton afferents innervating type II hair cells, and afferent calyces innervating type I hair cells. Electrical stimulation of VENs releases acetylcholine (ACh) at these synapses to exert diverse effects on afferent background discharge including rapid inhibition of bouton afferents and excitation of calyx-bearing afferents. Efferent-mediated inhibition is most pronounced in bouton afferents innervating type II hair cells near the torus, but becomes progressively smaller and briefer when moving longitudinally through the crista toward afferents innervating the planum...
2017: Frontiers in Cellular Neuroscience
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
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
H K Fan, T X Luo, W D Zhao, Y H Mu, Y Yang, W J Guo, H Y Tu, Q 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 crosstalk between extracellular Ca2+ entry and intracellular Ca2+ release. The small-conductance Ca2+ -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...
March 2018: Acta Physiologica
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)...
January 5, 2018: European Journal of Pharmacology
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
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
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 Ca2+-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
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
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
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