scholarly journals Molecular mechanisms of regulation of fast-inactivating voltage-dependent transient outward K+current in mouse heart by cell volume changes

2005 ◽  
Vol 568 (2) ◽  
pp. 423-443 ◽  
Author(s):  
Guan-Lei Wang ◽  
Ge-Xin Wang ◽  
Shintaro Yamamoto ◽  
Linda Ye ◽  
Heather Baxter ◽  
...  
Keyword(s):  
Cell Volume ◽  
Molecular Mechanisms ◽  
Mouse Heart ◽  
Volume Changes ◽  
Voltage Dependent ◽  
K Current

scholarly journals Physiological Roles of the Rapidly Activated Delayed Rectifier K+ Current in Adult Mouse Heart Primary Pacemaker Activity

2021 ◽  
Vol 22 (9) ◽  
pp. 4761
Author(s):  
Wei Hu ◽  
Robert B. Clark ◽  
Wayne R. Giles ◽  
Erwin Shibata ◽  
Henggui Zhang
Keyword(s):  
Adult Mouse ◽  
Delayed Rectifier ◽  
Pacemaker Activity ◽  
Mouse Heart ◽  
Voltage Dependent ◽  
Electrophysiological Studies ◽  
Ionic Mechanisms ◽  
K Current ◽  
Significant Expression

Robust, spontaneous pacemaker activity originating in the sinoatrial node (SAN) of the heart is essential for cardiovascular function. Anatomical, electrophysiological, and molecular methods as well as mathematical modeling approaches have quite thoroughly characterized the transmembrane fluxes of Na+, K+ and Ca2+ that produce SAN action potentials (AP) and ‘pacemaker depolarizations’ in a number of different in vitro adult mammalian heart preparations. Possible ionic mechanisms that are responsible for SAN primary pacemaker activity are described in terms of: (i) a Ca2+-regulated mechanism based on a requirement for phasic release of Ca2+ from intracellular stores and activation of an inward current-mediated by Na+/Ca2+ exchange; (ii) time- and voltage-dependent activation of Na+ or Ca2+ currents, as well as a cyclic nucleotide-activated current, If; and/or (iii) a combination of (i) and (ii). Electrophysiological studies of single spontaneously active SAN myocytes in both adult mouse and rabbit hearts consistently reveal significant expression of a rapidly activating time- and voltage-dependent K+ current, often denoted IKr, that is selectively expressed in the leading or primary pacemaker region of the adult mouse SAN. The main goal of the present study was to examine by combined experimental and simulation approaches the functional or physiological roles of this K+ current in the pacemaker activity. Our patch clamp data of mouse SAN myocytes on the effects of a pharmacological blocker, E4031, revealed that a rapidly activating K+ current is essential for action potential (AP) repolarization, and its deactivation during the pacemaker potential contributes a small but significant component to the pacemaker depolarization. Mathematical simulations using a murine SAN AP model confirm that well known biophysical properties of a delayed rectifier K+ current can contribute to its role in generating spontaneous myogenic activity.

Liver cell hydration and integrin signaling

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Bonus ◽  
Dieter Häussinger ◽  
Holger Gohlke
Keyword(s):  
Cell Volume ◽  
Liver Cell ◽  
Cell Function ◽  
The Other ◽  
Signaling Cascades ◽  
Integrin Signaling ◽  
Volume Changes ◽  
The One ◽  
And Oxidative Stress

Abstract Liver cell hydration (cell volume) is dynamic and can change within minutes under the influence of hormones, nutrients, and oxidative stress. Such volume changes were identified as a novel and important modulator of cell function. It provides an early example for the interaction between a physical parameter (cell volume) on the one hand and metabolism, transport, and gene expression on the other. Such events involve mechanotransduction (osmosensing) which triggers signaling cascades towards liver function (osmosignaling). This article reviews our own work on this topic with emphasis on the role of β1 integrins as (osmo-)mechanosensors in the liver, but also on their role in bile acid signaling.

scholarly journals Gonadotropin-Releasing Hormone Inhibits Ether-à-Go-Go-Related Gene K+ Currents in Mouse Gonadotropes

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1079-1088 ◽  
Author(s):  
Wiebke Hirdes ◽  
Crenguta Dinu ◽  
Christiane K. Bauer ◽  
Ulrich Boehm ◽  
Jürgen R. Schwarz
Keyword(s):  
Resting Potential ◽  
Related Gene ◽  
Activation Curve ◽  
Signal Cascade ◽  
Primary Mouse ◽  
Voltage Dependent ◽  
K Current ◽  
Unknown Signal ◽  
Ca2 Channels ◽  
K Currents

Secretion of LH from gonadotropes is initiated by a GnRH-induced increase in intracellular Ca2+ concentration ([Ca2+]i). This increase in [Ca2+]i is the result of Ca2+ release from intracellular stores and Ca2+ influx through voltage-dependent Ca2+ channels. Here we describe an ether-à-go-go-related gene (erg) K+ current in primary mouse gonadotropes and its possible function in the control of Ca2+ influx. To detect gonadotropes, we used a knock-in mouse strain, in which GnRH receptor-expressing cells are fluorescently labeled. Erg K+ currents were recorded in 80–90% of gonadotropes. Blockage of erg currents by E-4031 depolarized the resting potential by 5–8 mV and led to an increase in [Ca2+]i, which was abolished by nifedipine. GnRH inhibited erg currents by a reduction of the maximal erg current and in some cells additionally by a shift of the activation curve to more positive potentials. In conclusion, the erg current contributes to the maintenance of the resting potential in gonadotropes, thereby securing a low [Ca2+]i by restricting Ca2+ influx. In addition, the erg channels are modulated by GnRH by an as-yet unknown signal cascade.

Polymer inaccessible volume changes during opening and closing of a voltage-dependent ionic channel

Nature ◽  
1986 ◽  
Vol 323 (6083) ◽  
pp. 36-39 ◽  
Author(s):  
Joshua Zimmerberg ◽  
V. Adrian Parsegian
Keyword(s):  
Ionic Channel ◽  
Volume Changes ◽  
Voltage Dependent ◽  
Opening And Closing

Pharmacological mechanism of topiramate in the prophylaxis and treatment of migraine: a review

2018 ◽  
pp. 190-195
Author(s):  
Emanuela Paz Rosas ◽  
Raisa Ferreira Costa ◽  
Silvania Tavares Paz ◽  
Ana Paula Fernandes da Silva ◽  
Manuela Freitas Lyra de Freitas
Keyword(s):  
Cortical Spreading Depression ◽  
Molecular Mechanisms ◽  
Spreading Depression ◽  
Neuronal Excitability ◽  
Mechanisms Of Action ◽  
World Population ◽  
Gamma Aminobutyric Acid ◽  
Pharmacological Mechanism ◽  
Calcium Ion Channels ◽  
Voltage Dependent

Objective: This review sought to bring evidence of studies addressing the mechanisms of action of topiramate in the prevention and treatment of migraine. Background: Migraine is a neurovascular disorder that affects a large part of the world population. The use of prophylactics contributes to the decrease in the frequency and severity of this disease. Among the antiepileptic drugs, the topiramate, has proven to be the most effective for the treatment of migraine. Although the mechanism of action of this drug is still not well elucidated in the literature, there are several molecular mechanisms proposed. Methodology: A survey was carried out in the literature, from February to March 2018, in different databases, using the descriptors: topiramate, migraine and mechanisms of action. After a careful selection, 25 manuscripts were chosen for this review. Results: Evidence from a number of studies has indicated that the main mechanisms of action of topiramate are related to the modulation of voltage-dependent sodium and calcium ion channels, blockade of excitatory glutamate transmission and inhibition by gamma-aminobutyric acid receptors (GABA), AMPA/kainate and some isoenzymes of carbonic anhydrase. In addition, topiramate is involved in the suppression of cortical spreading depression, besides influencing trigeminovascular activity, and neuronal excitability. Conclusion: Thus, topiramate could be involved in the prevention of major events of the pathophysiology of migraine. Acting directly on cortical spreading depression (DAC), trigeminovascular signals and decreased central sensitization of migraine pain.

Cell volume changes affect gluconeogenesis in the perfused liver of the catfishClarias batrachus

2004 ◽  
Vol 29 (3) ◽  
pp. 337-347 ◽  
Author(s):  
Carina Goswami ◽  
Shritapa Datta ◽  
Kuheli Biswas ◽  
Nirmalendu Saha
Keyword(s):  
Cell Volume ◽  
Perfused Liver ◽  
Volume Changes

Reduction of voltage-activated K+ currents by forskolin is not mediated via cAMP in pleural sensory neurons of Aplysia

1990 ◽  
Vol 64 (5) ◽  
pp. 1474-1483 ◽  
Author(s):  
D. A. Baxter ◽  
J. H. Byrne
Keyword(s):  
Adenylate Cyclase ◽  
Sensory Neurons ◽  
Water Solubility ◽  
Membrane Current ◽  
Peak Amplitude ◽  
Bath Application ◽  
Voltage Dependent ◽  
K Current ◽  
Derivatives Of ◽  
K Currents

1. Forskolin is often used to activate adenylate cyclase in studies relating adenosine 3',5'-cyclic monophosphate (cAMP) to the modulation of membrane current. There is growing concern, however, that some actions of forskolin are independent of cAMP. With the use of two-electrode voltage-clamp techniques, we compared the effects of analogues of cAMP to the effects of forskolin on K+ currents in somata of sensory neurons that were isolated from pleural ganglia of Aplysia californica. 2. Analogues of cAMP did not reduce the peak amplitude of either the transient K+ current (IA) or the voltage-dependent K+ current (IK.V). Analogues of cAMP did reduce the previously described cAMP-sensitive S K+ current (IK.S). In contrast, forskolin reduced the peak amplitude of both IA and IK.V. Furthermore, both IA and IK.V were reduced by 1,9-dideoxy-forskolin, a derivative of forskolin that does not activate adenylate cyclase. These results indicate that the effects of forskolin and 1,9-dideoxy-forskolin on IA and IK.V were not mediated via cAMP. 3. Bath application of a modified form of forskolin (7-deacetyl-6-[N-acetylglycyl]-forskolin), which has enhanced water solubility and activates adenylate cyclase, reduced IK.S, but did not alter either IA or IK.V. Thus it appears that certain derivatives of forskolin can be used to activate adenylate cyclase and avoid some of the nonspecific actions on membrane current that are associated with forskolin.

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