scholarly journals Cell-Type-Independent Expression of Inwardly Rectifying Potassium Currents in Mouse Fungiform Taste Bud Cells

2020 ◽  
pp. 501-510
Author(s):  
Y NAKAO ◽  
M KOSHIMURA ◽  
T YAMASAKI ◽  
Y OHTUBO
Keyword(s):  
Membrane Potential ◽  
Cell Types ◽  
Taste Bud ◽  
Resting Membrane Potential ◽  
Type I ◽  
Cell Type ◽  
Kir Channels ◽  
Current Densities ◽  
Inwardly Rectifying ◽  
Taste Bud Cells

Inwardly rectifying potassium (Kir) channels play key roles in functions, including maintaining the resting membrane potential and regulating the action potential duration in excitable cells. Using in situ whole-cell recordings, we investigated Kir currents in mouse fungiform taste bud cells (TBCs) and immunologically identified the cell types (type I-III) expressing these currents. We demonstrated that Kir currents occur in a cell-type-independent manner. The activation potentials we measured were -80 to -90 mV, and the magnitude of the currents increased as the membrane potentials decreased, irrespective of the cell types. The maximum current densities at -120 mV showed no significant differences among cell types (p>0.05, one-way ANOVA). The density of Kir currents was not correlated with the density of either transient inward currents or outwardly rectifying currents, although there was significant correlation between transient inward and outwardly rectifying current densities (p<0.05, test for no correlation). RT-PCR studies employing total RNA extracted from peeled lingual epithelia detected mRNAs for Kir1, Kir2, Kir4, Kir6, and Kir7 families. These findings indicate that TBCs express several types of Kir channels functionally, which may contribute to regulation of the resting membrane potential and signal transduction of taste.

scholarly journals Expression, localization, and functional properties of inwardly rectifying K+ channels in the kidney

2020 ◽  
Vol 318 (2) ◽  
pp. F332-F337 ◽  
Author(s):  
Anna D. Manis ◽  
Matthew R. Hodges ◽  
Alexander Staruschenko ◽  
Oleg Palygin
Keyword(s):  
Membrane Potential ◽  
Ion Transport ◽  
Functional Properties ◽  
Current Knowledge ◽  
Cell Types ◽  
Resting Membrane Potential ◽  
K Channels ◽  
Multiple Organs ◽  
Inwardly Rectifying ◽  
Made In

Inwardly rectifying K+ (Kir) channels are expressed in multiple organs and cell types and play critical roles in cellular function. Most notably, Kir channels are major determinants of the resting membrane potential and K+ homeostasis. The renal outer medullary K+ channel (Kir1.1) was the first renal Kir channel identified and cloned in the kidney over two decades ago. Since then, several additional members, including classical and ATP-regulated Kir family classes, have been identified to be expressed in the kidney and to contribute to renal ion transport. Although the ATP-regulated Kir channel class remains the most well known due to severe pathological phenotypes associated with their mutations, progress is being made in defining the properties, localization, and physiological functions of other renal Kir channels, including those localized to the basolateral epithelium. This review is primarily focused on the current knowledge of the expression and localization of renal Kir channels but will also briefly describe their proposed functions in the kidney.

Some Observations on Changes in Denervated Taste Buds of Circumvallate Papillae of Rabbits

1969 ◽  
Vol 27 ◽  
pp. 308-309
Author(s):  
Sunao Fujimoto ◽  
Raymond G. Murray ◽  
Assia Murray
Keyword(s):  
Taste Buds ◽  
Taste Bud ◽  
Cell Type ◽  
Dark Cells ◽  
Type Iii ◽  
Circumvallate Papillae ◽  
Taste Bud Cells ◽  
Light Cells

Taste bud cells in circumvallate papillae of rabbit have been classified into three groups: dark cells; light cells; and type III cells. Unilateral section of the 9th nerve distal to the petrosal ganglion was performed in 18 animals, and changes of each cell type in the denervated buds were observed from 6 hours to 10 days after the operation.Degeneration of nerves is evident at 12 hours (Fig. 1) and by 2 days, nerves are completely lacking in the buds. Invasion by leucocytes into the buds is remarkable from 6 to 12 hours but then decreases. Their extrusion through the pore is seen. Shrinkage and disturbance in arrangement of cells in the buds can be seen at 2 days. Degenerated buds consisting of a few irregular cells and remnants of degenerated cells are present at 4 days, but buds apparently normal except for the loss of nerve elements are still present at 6 days.

Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

2007 ◽  
Vol 292 (1) ◽  
pp. R388-R395 ◽  
Author(s):  
Cristina E. Molina ◽  
Hans Gesser ◽  
Anna Llach ◽  
Lluis Tort ◽  
Leif Hove-Madsen
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Atrial Myocytes ◽  
Atrial Tissue ◽  
Isolated Cardiac Myocytes ◽  
Inwardly Rectifying

Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current ( Im) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of −87 ± 2 mV and −83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at −120 mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from −78 ± 3 to −84 ± 3 mV, and stabilized the resting membrane potential at −92 ± 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or Im in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Transmitter Regulation of Plateau Properties in Turtle Motoneurons

1998 ◽  
Vol 79 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Gytis Svirskis ◽  
Jørn Hounsgaard
Keyword(s):  
Membrane Potential ◽  
Metabotropic Glutamate Receptors ◽  
Input Resistance ◽  
Pattern Generation ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Type I ◽  
Plateau Potentials ◽  
Inward Current

Svirskis, Gytis and Jørn Hounsgaard. Transmitter regulation of plateau properties in turtle motoneurons. J. Neurophysiol. 79: 45–50, 1998. In motoneurons, generation of plateau potentials is promoted by modulators that block potassium channels. In voltage-clamp experiments with triangular voltage ramp commands, we show that cis-(±)-1-aminocyclopentane-1,3-dicarboxylic acid ( cis-ACPD) and muscarine promote the generation of plateau potentials by increasing the dihydropyridine sensitive inward current, by increasing the input resistance, and by depolarizing the resting membrane potential. Type I metabotropic glutamate receptors (mGluR I) mediate the effects of cis-ACPD. Baclofen suppresses generation of plateau potentials by decreasing the dihydropyridine sensitive inward current, by decreasing the input resistance, and by hyperpolarizing the resting membrane potential. These results suggest that membrane properties of motoneurons are continuously modulated by synaptic activity in ways that may have profound effects on synaptic integration and pattern generation.

scholarly journals A High-Throughput Electrophysiology Assay Identifies Inhibitors of the Inwardly Rectifying Potassium Channel Kir7.1

2015 ◽  
Vol 20 (6) ◽  
pp. 739-747 ◽  
Author(s):  
Paul D. Wright ◽  
Srinivasan Kanumilli ◽  
David Tickle ◽  
Jamie Cartland ◽  
Nathalie Bouloc ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Potassium Channel ◽  
Screening Strategy ◽  
Resting Membrane Potential ◽  
Pharmacological Characterization ◽  
Inwardly Rectifying Potassium Channel ◽  
A Cell ◽  
Automated Patch Clamp ◽  
Patch Clamp Electrophysiology ◽  
Inwardly Rectifying

Kir7.1 is an inwardly rectifying potassium channel that has been implicated in controlling the resting membrane potential of the myometrium. Abnormal uterine activity in pregnancy plays an important role in postpartum hemorrhage, and novel therapies for this condition may lie in manipulation of membrane potential. This work presents an assay development and screening strategy for identifying novel inhibitors of Kir7.1. A cell-based automated patch-clamp electrophysiology assay was developed using the IonWorks Quattro (Molecular Devices, Sunnyvale, CA) system, and the iterative optimization is described. In total, 7087 compounds were tested, with a hit rate (>40% inhibition) of 3.09%. During screening, average Z′ values of 0.63 ± 0.09 were observed. After chemistry triage, lead compounds were resynthesized and activity confirmed by IC50 determinations. The most potent compound identified (MRT00200769) gave rise to an IC50 of 1.3 µM at Kir7.1. Compounds were assessed for selectivity using the inwardly rectifying potassium channel Kir1.1 (ROMK) and hERG (human Ether-à-go-go Related Gene). Pharmacological characterization of known Kir7.1 inhibitors was also carried out and analogues of VU590 tested to assess selectivity at Kir7.1.

scholarly journals K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts

2005 ◽  
Vol 288 (6) ◽  
pp. H2931-H2939 ◽  
Author(s):  
L. Chilton ◽  
S. Ohya ◽  
D. Freed ◽  
E. George ◽  
V. Drobic ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Reversal Potential ◽  
Mechanical Activity ◽  
Resting Membrane Potential ◽  
Whole Cell Patch Clamp ◽  
Voltage Dependent ◽  
Primary Determinant ◽  
Inwardly Rectifying ◽  
Low K ◽  
Ionic Basis

Despite the important roles played by ventricular fibroblasts and myofibroblasts in the formation and maintenance of the extracellular matrix, neither the ionic basis for membrane potential nor the effect of modulating membrane potential on function has been analyzed in detail. In this study, whole cell patch-clamp experiments were done using ventricular fibroblasts and myofibroblasts. Time- and voltage-dependent outward K+ currents were recorded at depolarized potentials, and an inwardly rectifying K+ (Kir) current was recorded near the resting membrane potential (RMP) and at more hyperpolarized potentials. The apparent reversal potential of Kir currents shifted to more positive potentials as the external K+ concentration ([K+]o) was raised, and this Kir current was blocked by 100–300 μM Ba2+. RT-PCR measurements showed that mRNA for Kir2.1 was expressed. Accordingly, we conclude that Kir current is a primary determinant of RMP in both fibroblasts and myofibroblasts. Changes in [K+]o influenced fibroblast membrane potential as well as proliferation and contractile functions. Recordings made with a voltage-sensitive dye, DiBAC3(4), showed that 1.5 mM [K+]o resulted in a hyperpolarization, whereas 20 mM [K+]o produced a depolarization. Low [K+]o (1.5 mM) enhanced myofibroblast number relative to control (5.4 mM [K+]o). In contrast, 20 mM [K+]o resulted in a significant reduction in myofibroblast number. In separate assays, 20 mM [K+]o significantly enhanced contraction of collagen I gels seeded with myofibroblasts compared with control mechanical activity in 5.4 mM [K+]o. In combination, these results show that ventricular fibroblasts and myofibroblasts express a variety of K+ channel α-subunits and demonstrate that Kir current can modulate RMP and alter essential physiological functions.

ATP-sensitive and inwardly rectifying potassium channels in smooth muscle

1997 ◽  
Vol 77 (4) ◽  
pp. 1165-1232 ◽  
Author(s):  
J. M. Quayle ◽  
M. T. Nelson ◽  
N. B. Standen
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Protein Kinase ◽  
Potassium Channels ◽  
Membrane Conductance ◽  
Katp Channels ◽  
Muscle Membrane ◽  
Sulfonylurea Receptor ◽  
Kir Channels ◽  
Inwardly Rectifying

The properties and roles of ATP-sensitive (KATP) and inwardly rectifying (KIR) potassium channels are reviewed. Potassium channels regulate the membrane potential of smooth muscle, which controls calcium entry through voltage-dependent calcium channels, and thereby contractility through changes in intracellular calcium. The KATP channel is likely to be composed of members of the inward rectifier channel gene family (Kir6) and sulfonylurea receptor proteins. The KIR channels do not appear to be as widely distributed as KATP channels in smooth muscle and may provide a mechanism by which changes in extracellular K+ can alter smooth muscle membrane potential, and thereby arterial diameter. The KATP channels contribute to the resting membrane conductance of some types of smooth muscle and can open under situations of metabolic compromise. The KATP channels are targets of a wide variety of vasodilators and constrictors, which act, respectively, through adenosine 3',5'-cyclic monophosphate/protein kinase A and protein kinase C. The KATP channels are also activated by a number of synthetic vasodilators (e.g., diazoxide and pinacidil) and are inhibited by the oral hypoglycemic sulfonylurea drugs (e.g., glibenclamide). Together, KATP and KIR channels are important regulators of smooth muscle function and represent important therapeutic targets.

scholarly journals Cell type-specific membrane potential changes in dorsolateral striatum accompanying reward-based sensorimotor learning

Function ◽  
2021 ◽  
Author(s):  
Tanya Sippy ◽  
Corryn Chaimowitz ◽  
Sylvain Crochet ◽  
Carl C H Petersen
Keyword(s):  
Membrane Potential ◽  
Dopamine Receptors ◽  
Cell Types ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Cell Type ◽  
Indirect Pathway ◽  
Cell Type Specific ◽  
Striatal Membrane ◽  
Sensory Evoked

Abstract The striatum integrates sensorimotor and motivational signals, likely playing a key role in reward-based learning of goal-directed behavior. However, cell type-specific mechanisms underlying reinforcement learning remain to be precisely determined. Here, we investigated changes in membrane potential dynamics of dorsolateral striatal neurons comparing naïve mice and expert mice trained to lick a reward spout in response to whisker deflection. We recorded from three distinct cell types: i) direct pathway striatonigral neurons, which express type 1 dopamine receptors; ii) indirect pathway striatopallidal neurons, which express type 2 dopamine receptors; and iii) tonically active, putative cholinergic, striatal neurons. Task learning was accompanied by cell type-specific changes in the membrane potential dynamics evoked by the whisker deflection and licking in successfully-performed trials. Both striatonigral and striatopallidal types of striatal projection neurons showed enhanced task-related depolarization across learning. Striatonigral neurons showed a prominent increase in a short latency sensory-evoked depolarization in expert compared to naïve mice. In contrast, the putative cholinergic striatal neurons developed a hyperpolarizing response across learning, driving a pause in their firing. Our results reveal cell type-specific changes in striatal membrane potential dynamics across the learning of a simple goal-directed sensorimotor transformation, helpful for furthering the understanding of the various potential roles of different basal ganglia circuits.

scholarly journals Hypothesis-free identification of modulators of genetic risk factors

2015 ◽  
Author(s):  
Daria Zhernakova ◽  
Patrick Deelen ◽  
Martijn Vermaat ◽  
Maarten van Iterson ◽  
Michiel van Galen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Regulatory Networks ◽  
Large Scale ◽  
Cell Types ◽  
Genetic Risk Factors ◽  
Type I ◽  
Cell Type ◽  
Disease Etiology ◽  
Context Dependent

Genetic risk factors often localize in non-coding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying the association of genetic risk factors with disease. More mechanistic insights can be derived from knowledge of the context, such as cell type or the activity of signaling pathways, influencing the nature and strength of eQTLs. Here, we generated peripheral blood RNA-seq data from 2,116 unrelated Dutch individuals and systematically identified these context-dependent eQTLs using a hypothesis-free strategy that does not require prior knowledge on the identity of the modifiers. Out of the 23,060 significant cis-regulated genes (false discovery rate ≤ 0.05), 2,743 genes (12%) show context-dependent eQTL effects. The majority of those were influenced by cell type composition, revealing eQTLs that are particularly strong in cell types such as CD4+ T-cells, erythrocytes, and even lowly abundant eosinophils. A set of 145 cis-eQTLs were influenced by the activity of the type I interferon signaling pathway and we identified several cis-eQTLs that are modulated by specific transcription factors that bind to the eQTL SNPs. This demonstrates that large-scale eQTL studies in unchallenged individuals can complement perturbation experiments to gain better insight in regulatory networks and their stimuli.

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