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https://www.readbyqxmd.com/read/29897864/calcium-induced-calcium-release-activates-spontaneous-miniature-outward-currents-in-newt-medullary-reticular-formation-neurons
#1
Daniel B Yaeger, Emma J Coddington
Neurons in the medullary reticular formation are involved in the control of postural and locomotor behaviors in all vertebrates. Reticulospinal neurons in this brain region provide one of the major descending projections to the spinal cord. Although neurons in the newt medullary reticular formation have been extensively studied using in vivo extracellular recordings, little is known of their intrinsic biophysical properties or of the underlying circuitry of this region. Using whole-cell patch-clamp recordings in brain slices containing the rostromedial reticular formation (rmRF) from adult male newts, we observed spontaneous miniature outward currents (SMOCs) in approximately two-thirds of neurons...
June 13, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29852172/activation-of-galanin-receptor-1-inhibits-locus-coeruleus-neurons-via-girk-channels
#2
Yun-Fei Bai, Hai-Tao Ma, Li-Na Liu, Hui Li, Xiao-Xiao Li, Yu-Tao Yang, Bing Xue, Di Wang, Zhi-Qing David Xu
The noradrenergic neurons of the locus coeruleus (LC) are associated with various brain functions and psychiatric disorders, such as addiction and depression. It has been shown that neuropeptide galanin (GAL) inhibits neuronal excitability in LC, but the mechanisms remain unclear. In the present study, we investigated the ionic and signal transduction mechanisms underlying inhibitory effect of GAL on LC neurons using whole-cell patch clamp recording in rat brain slices. Bath application of GAL decreased the spontaneous firings and induced a dose-dependent hyperpolarization of LC neurons and this effect was attenuated by knockdown of Galr1, but not Galr2, confirming that mainly GALR1 mediates the inhibition effect of GAL...
May 28, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29850792/downregulation-of-bk-channel-function-and-protein-expression-in-coronary-arteriolar-smooth-muscle-cells-of-type-2-diabetic-patients
#3
Tong Lu, Qiang Chai, Guoqing Jiao, Xiao-Li Wang, Xiaojing Sun, Jonathan D Furuseth, John M Stulak, Richard C Daly, Kevin L Greason, Yong-Mei Cha, Hon-Chi Lee
Aims: Type 2 diabetes (T2D) is strongly associated with cardiovascular morbidity and mortality in patients. Vascular large conductance Ca2+-activated potassium (BK) channels, composed of four pore-forming α subunits (BK-α) and four regulatory β1 subunits (BK-β1), are densely expressed in coronary arterial smooth muscle cells (SMCs) and play an important role in regulating vascular tone and myocardial perfusion. However, the role of BK channels in coronary microvascular dysfunction of human subjects with diabetes is unclear...
May 30, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29847609/dendritic-potassium-channel-dysfunction-may-contribute-to-dendrite-degeneration-in-spinocerebellar-ataxia-type-1
#4
Ravi Chopra, David D Bushart, Vikram G Shakkottai
Purkinje neuron dendritic degeneration precedes cell loss in cerebellar ataxia, but the basis for dendritic vulnerability in ataxia remains poorly understood. Recent work has suggested that potassium (K+) channel dysfunction and consequent spiking abnormalities contribute to Purkinje neuron degeneration, but little attention has been paid to how K+ channel dysfunction impacts dendritic excitability and the role this may play in the degenerative process. We examined the relationship between K+ channel dysfunction, dendritic excitability and dendritic degeneration in spinocerebellar ataxia type 1 (SCA1)...
2018: PloS One
https://www.readbyqxmd.com/read/29770866/meucin-49-a-multifunctional-scorpion-venom-peptide-with-bactericidal-synergy-with-neurotoxins
#5
Bin Gao, Julie Dalziel, Simone Tanzi, Shunyi Zhu
Besides key roles in prey capture and predator defense, scorpion venom also functions as internal immune agents protecting the venom gland from infection and external immune agents cleaning saprophytic microbes from their own body surfaces. However, antimicrobials (typically antimicrobial peptides, AMPs) in the venom often exist in low abundance that might exclude their immune role alone, leaving an open question with regard to their in vivo biological function. Here, we report the bactericidal activity of seven peptides isolated from the scorpion Mesobuthus eupeus venom, including one classical α-helical AMP and five ion channel-targeted neurotoxins...
May 16, 2018: Amino Acids
https://www.readbyqxmd.com/read/29767559/g-protein-pathway-suppressor-2-gps2-enhanced-the-renal-large-conductance-ca2-activated-potassium-channel-expression-via-inhibiting-erk-1-2-signaling-pathway
#6
Zhizhi Zhuang, Jia Xiao, Xinxin Chen, Xiaohan Hu, Ruidian Li, Shan Chen, Xiuyan Feng, Saier Shen, He-Ping Ma, Jieqiu Zhuang, Hui Cai
G-protein pathway suppressor 2 (GPS2) is a multifunctional protein and transcriptional regulation factor that is involved in the G-protein mitogen-activated protein kinase (MAPK) signaling pathway. It has been shown that the MAPK signaling pathway plays an important role in the regulation of renal large conductance Ca2+ activated potassium (BK) channels. In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. In HEK BK stably-expressing cells transfected with either GPS2 or its pCMV vector control, a single cell recording showed that GPS2 significantly increased BK channel activity (NPo), increasing BK open probability (Po) and channel number (N) compared to the control...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29760657/purkinje-cell-signaling-deficits-in-animal-models-of-ataxia
#7
REVIEW
Eriola Hoxha, Ilaria Balbo, Maria Concetta Miniaci, Filippo Tempia
Purkinje cell (PC) dysfunction or degeneration is the most frequent finding in animal models with ataxic symptoms. Mutations affecting intrinsic membrane properties can lead to ataxia by altering the firing rate of PCs or their firing pattern. However, the relationship between specific firing alterations and motor symptoms is not yet clear, and in some cases PC dysfunction precedes the onset of ataxic signs. Moreover, a great variety of ionic and synaptic mechanisms can affect PC signaling, resulting in different features of motor dysfunction...
2018: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29751615/the-maxi-k-bk-channel-antagonist-penitrem-a-as-a-novel-breast-cancer-targeted-therapeutic
#8
Amira A Goda, Abu Bakar Siddique, Mohamed Mohyeldin, Nehad M Ayoub, Khalid A El Sayed
Breast cancer (BC) is a heterogeneous disease with different molecular subtypes. The high conductance calcium-activated potassium channels (BK, Maxi-K channels) play an important role in the survival of some BC phenotypes, via membrane hyperpolarization and regulation of cell cycle. BK channels have been implicated in BC cell proliferation and invasion. Penitrems are indole diterpene alkaloids produced by various terrestrial and marine Penicillium species. Penitrem A ( 1 ) is a selective BK channel antagonist with reported antiproliferative and anti-invasive activities against multiple malignancies, including BC...
May 11, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29748711/calcium-and-voltage-gated-bk-channels-in-vascular-smooth-muscle
#9
REVIEW
Alex M Dopico, Anna N Bukiya, Jonathan H Jaggar
Ion channels in vascular smooth muscle regulate myogenic tone and vessel contractility. In particular, activation of calcium- and voltage-gated potassium channels of large conductance (BK channels) results in outward current that shifts the membrane potential toward more negative values, triggering a negative feed-back loop on depolarization-induced calcium influx and SM contraction. In this short review, we first present the molecular basis of vascular smooth muscle BK channels and the role of subunit composition and trafficking in the regulation of myogenic tone and vascular contractility...
May 11, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29740284/ionic-mechanism-underlying-rebound-depolarization-in-medial-prefrontal-cortex-pyramidal-neurons
#10
Przemysław Kurowski, Katarzyna Grzelka, Paweł Szulczyk
Rebound depolarization (RD) occurs after membrane hyperpolarization and converts an arriving inhibitory signal into cell excitation. The purpose of our study was to clarify the ionic mechanism of RD in synaptically isolated layer V medial prefrontal cortex (mPFC) pyramidal neurons in slices obtained from 58- to 62-day-old male rats. The RD was evoked after a step hyperpolarization below -80 mV, longer than 150 ms in 192 of 211 (91%) tested neurons. The amplitude of RD was 30.6 ± 1.2 mV above the resting membrane potential (-67...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29706583/serotonergic-signaling-controls-input-specific-synaptic-plasticity-at-striatal-circuits
#11
Anna Cavaccini, Marta Gritti, Andrea Giorgi, Andrea Locarno, Nicolas Heck, Sara Migliarini, Alice Bertero, Maddalena Mereu, Giulia Margiani, Massimo Trusel, Tiziano Catelani, Roberto Marotta, Maria Antonietta De Luca, Jocelyne Caboche, Alessandro Gozzi, Massimo Pasqualetti, Raffaella Tonini
Monoaminergic modulation of cortical and thalamic inputs to the dorsal striatum (DS) is crucial for reward-based learning and action control. While dopamine has been extensively investigated in this context, the synaptic effects of serotonin (5-HT) have been largely unexplored. Here, we investigated how serotonergic signaling affects associative plasticity at glutamatergic synapses on the striatal projection neurons of the direct pathway (dSPNs). Combining chemogenetic and optogenetic approaches reveals that impeding serotonergic signaling preferentially gates spike-timing-dependent long-term depression (t-LTD) at thalamostriatal synapses...
May 16, 2018: Neuron
https://www.readbyqxmd.com/read/29705199/determination-of-the-stoichiometry-between-%C3%AE-and-%C3%AE-1-subunits-of-the-bk-channel-using-lret
#12
Willy Carrasquel-Ursulaez, Osvaldo Alvarez, Francisco Bezanilla, Ramon Latorre
Two families of accessory proteins, β and γ, modulate BK channel gating and pharmacology. Notably, in the absence of internal Ca2+ , the γ1 subunit promotes a large shift of the BK conductance-voltage curve to more negative potentials. However, very little is known about how α- and γ1 subunits interact. In particular, the association stoichiometry between both subunits is unknown. Here, we propose a method to answer this question using lanthanide resonance energy transfer. The method assumes that the kinetics of lanthanide resonance energy transfer-sensitized emission of the donor double-labeled α/γ1 complex is the linear combination of the kinetics of the sensitized emission in single-labeled complexes...
April 25, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29698749/the-role-of-ca-2-and-bk-channels-of-locus-coeruleus-lc-neurons-as-a-brake-to-the-co-2-chemosensitivity-response-of-rats
#13
Ann N Imber, Luis G A Patrone, Ke-Yong Li, Luciane H Gargaglioni, Robert W Putnam
The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an "accelerator" whereby hypercapnic acidosis causes an inhibition of K+ channels or activation of Na+ and Ca+2 channels to depolarize CO2 -sensitive neurons. Nevertheless, it is still unknown if this "accelerator" mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons...
April 24, 2018: Neuroscience
https://www.readbyqxmd.com/read/29649319/unraveling-endothelin-1-induced-hypercontractility-of-human-pulmonary-artery-smooth-muscle-cells-from-patients-with-pulmonary-arterial-hypertension
#14
Jamie L Wilson, Rod Warburton, Linda Taylor, Deniz Toksoz, Nicholas Hill, Peter Polgar
Contraction of human pulmonary artery smooth muscle cells (HPASMC) isolated from pulmonary arterial hypertensive (PAH) and normal (non-PAH) subject lungs was determined and measured with real-time electrical impedance. Treatment of HPASMC with vasoactive peptides, endothelin-1 (ET-1) and bradykinin (BK) but not angiotensin II, induced a temporal decrease in the electrical impedance profile mirroring constrictive morphological change of the cells which typically was more robust in PAH as opposed to non-PAH cells...
2018: PloS One
https://www.readbyqxmd.com/read/29623857/the-large-conductance-calcium-and-voltage-activated-potassium-channel-bk-and-epilepsy-a-short-review
#15
Kai Zang, Yuwen Zhang, Jie Hu, Yun Wang
The large conductance calcium- and voltage-activated potassium channels (BK) are a kind of widely distributed channel proteins which exist in virtually every cell type of mammals and function to influence membrane excitability and Ca2+ signaling. BK channels can be activated by the increase of the intracellular Ca2+ concentration, a consequence of neuronal excitation, and then terminate the action potential with the outward K+ flux. Moreover, after-hyperpolarization induced by BK channels closes Cav channels and thus precludes excessive Ca2+ influx...
April 3, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29596016/chronic-interval-exercise-training-prevents-bk-ca-channel-mediated-coronary-vascular-dysfunction-in-aortic-banded-mini-swine
#16
T Dylan Olver, Jenna C Edwards, Brian S Ferguson, Jessica A Hiemstra, Pamela K Thorne, Michael A Hill, Maurice Harold Laughlin, Craig A Emter
Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this study was to determine the therapeutic efficacy of chronic interval exercise training (IT) on BKCa channel-mediated coronary vascular function in heart failure. We hypothesized chronic interval exercise training would attenuate pressure overload-induced impairments to coronary BKCa channel-mediated function. A translational large animal model with cardiac features of heart failure with preserved ejection fraction was used to test this hypothesis...
March 29, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29574460/the-unexpected-role-of-calcium-activated-potassium-channels-limitation-of-no-induced-arterial-relaxation
#17
Johannes Schmid, Bettina Müller, David Heppeler, Dina Gaynullina, Mario Kassmann, Hristo Gagov, Mitko Mladenov, Maik Gollasch, Rudolf Schubert
BACKGROUND: Multiple studies have shown that an NO-induced activation of vascular smooth muscle BK channels contributes to the NO-evoked dilation in many blood vessels. In vivo, NO is released continuously. NO attenuates vessel constrictions and, therefore, exerts an anticontractile effect. It is unknown whether the anticontractile effect of continuously present NO is mediated by BK channels. METHODS AND RESULTS: This study tested the hypothesis that BK channels mediate the vasodilatory effect of continuously present NO...
March 24, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29545539/solution-structure-of-extracellular-loop-of-human-%C3%AE-4-subunit-of-bk-channel-and-its-biological-implication-on-chtx-sensitivity
#18
Yanting Wang, Wenxian Lan, Zhenzhen Yan, Jing Gao, Xinlian Liu, Sheng Wang, Xiying Guo, Chunxi Wang, Hu Zhou, Jiuping Ding, Chunyang Cao
Large-conductance Ca2+ - and voltage-dependent K+ (BK) channels display diverse biological functions while their pore-forming α subunit is coded by a single Slo1 gene. The variety of BK channels is correlated with the effects of BKα coexpression with auxiliary β (β1-β4) subunits, as well as newly defined γ subunits. Charybdotoxin (ChTX) blocks BK channel through physically occluding the K+ -conduction pore. Human brain enriched β4 subunit (hβ4) alters the conductance-voltage curve, slows activation and deactivation time courses of BK channels...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29545233/expanding-the-phenotype-of-homozygous-kcnma1-mutations-dyskinesia-epilepsy-intellectual-disability-cerebellar-and-corticospinal-tract-atrophy
#19
Gözde Yeşil, Ayşe Aralaşmak, Enes Akyüz, Dilara İçağasıoğlu, Türkan Uygur Şahin, Yavuz Bayram
BACKGROUND: The KCNMA1 gene encodes the α-subunit of the large conductance, voltage and calcium-sensitive potassium channel (BK channels) which plays an important role in neuronal excitability. Heterozygous mutations in KCNMA1 were firstly described in a large family with generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. Recently, homozygous KCNMA1 mutations were reported to cause a phenotype of cerebellar atrophy, developmental delay and seizures. CASE REPORT: Herein; we report a patient with a novel homozygous truncating mutation in KCNMA1 (p...
March 16, 2018: Balkan Medical Journal
https://www.readbyqxmd.com/read/29540546/regulation-of-nociceptive-glutamatergic-signaling-by-presynaptic-kv3-4-channels-in-the-rat-spinal-dorsal-horn
#20
Tanziyah Muqeem, Biswarup Ghosh, Vitor Pinto, Angelo C Lepore, Manuel Covarrubias
Presynaptic voltage-gated K+ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models...
April 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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