Maxi k channel

OBJECTIVES: To examine the effect of partial urethral obstruction (PUO) on bladder smooth muscle outward potassium current and the contribution of the large-conductance calcium-activated potassium (Maxi-K, BKCa) channel to this activity in smooth muscle cells isolated from bladders of sham-operated and PUO male rats using whole-cell patch clamp recording techniques. To determine the effect of PUO on the expression of the Maxi-K channel α and β1 subunits and in vitro detrusor contractility...

In developing kidneys, the total cell population is partly regulated by apoptosis. Despite our understanding of the molecular involvement in the regulatory pathway of apoptosis, we know little about the physiological involvement. Cardiomyocytes express large conductance voltage- and Ca(2+)-activated K(+) (maxi-K(+)) channels in their inner mitochondrial membranes. Triggering the mitochondrial K(+) influx necessary to inhibit apoptosis, the channels play cytoprotective roles during ischemic injury. Since proximal tubular cells in neonatal kidneys are physiologically under hypoxic stress, and since the channel activity is stimulated by hypoxia, those cells would share the same regulatory mechanism of apoptosis with ischemic cardiomyocytes...

Ca(2+) activation of Cl and K channels is a key event underlying stimulated fluid secretion from parotid salivary glands. Cl channels are exclusively present on the apical plasma membrane (PM), whereas the localization of K channels has not been established. Mathematical models have suggested that localization of some K channels to the apical PM is optimum for fluid secretion. A combination of whole cell electrophysiology and temporally resolved digital imaging with local manipulation of intracellular [Ca(2+)] was used to investigate if Ca(2+)-activated K channels are present in the apical PM of parotid acinar cells...

Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic swelling activates two types of macroscopic anion conductance with different voltage-dependence and pharmacology. At the single-channel level, we identified two types of events: one corresponded to the maxi-anion channel, and the other one had characteristics of the volume-sensitive outwardly rectifying (VSOR) chloride channel of intermediate conductance...

High-conductance calcium-activated potassium (Maxi-K) channels are present in smooth muscle where they regulate tone. Activation of Maxi-K channels causes smooth muscle hyperpolarization and shortening of action-potential duration, which would limit calcium entry through voltage-dependent calcium channels leading to relaxation. Although Maxi-K channels appear to indirectly mediate the relaxant effects of a number of agents, activators that bind directly to the channel with appropriate potency and pharmacological properties useful for proof-of-concept studies are not available...

Despite recent progress in physiology of fish ion homeostasis, the mechanism of plasma K+ regulation has remained unclear. Using Mozambique tilapia, a euryhaline teleost, we demonstrated that gill mitochondrion-rich (MR) cells were responsible for K+ excretion, using a newly invented technique that insolubilized and visualized K+ excreted from the gills. For a better understanding of the molecular mechanism of K+ excretion in the gills, cDNA sequences of renal outer medullary K+ channel (ROMK), potassium large conductance Ca(2+)-activated channel, subfamily M (Maxi-K), K(+)-Cl(-) cotransporters (KCC1, KCC2, and KCC4) were identified in tilapia as the candidate molecules that are involved in K+ handling...

Mitochondrial potassium channels are important mediators of cell protection against stress. The mitochondrial large-conductance "big" K(+) channel (mBK) mediates the evolutionarily-conserved process of anesthetic preconditioning (APC), wherein exposure to volatile anesthetics initiates protection against ischemic injury. Despite the role of the mBK in cardioprotection, the molecular identity of the channel remains unknown. We investigated the attributes of the mBK using C. elegans and mouse genetic models coupled with measurements of mitochondrial K(+) transport and APC...

Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium- and voltage-gated KCa1.1 channel (BK, Maxi-K, Slo1, KCNMA1) as the major potassium channel expressed at the plasma membrane of FLS isolated from patients with RA (RA-FLS). We further show that blocking this channel perturbs the calcium homeostasis of the cells and inhibits the proliferation, production of VEGF, IL-8, and pro-MMP-2, and migration and invasion of RA-FLS...

Maxi-K(+) (BK) channel diversity is attributed to alternative splicing in the kcnma1 gene. The resultant variants manifest themselves in different cell types, tissues, and functions, such as excitation, metabolism, and signaling. Immunoelectron microscopy revealed immunogold particle labeling of BK in apical and basal regions of inner and outer hair cells, respectively. Additional labeling occurs in Deiters' cells and the inner mitochondrial membrane. Identification of full-length sequences reveals 27 BK variants from embryonic and postnatal mouse inner ear, per classification by tail motif, VYR, DEC, and ERL, and by exon usage...

Large conductance potassium channels (BK(Ca) channels) play a central role in maintaining myometrial tone, thus activation of these channels proved to have therapeutic potential in preterm labor. Present study aims to unravel the presence of BK(Ca) (maxi-K) channels in buffalo myometrium. Tension experiments, mRNA and protein expression studies were done to characterize BK(Ca) channels in buffalo myometrium. Isolated myometrial preparations exhibited rhythmic spontaneity with regular pattern of amplitude and frequency...

INTRODUCTION: 1,2,4-triazoles and its derivatives have been reported to possess anti-inflammatory, analgesic, antimicrobial, anticancer, antitumor, antitubercular, anticonvulsant, openers of Ca-activated potassium (Maxi-K) channels, antiviral properties, hypoglycemic, anxiolytic and antidepressant activity. Therefore, 1,2,4-triazole seems to be an important pharmacophore. MATERIALS AND METHODS: The synthesis of 4-(substituted ethanoyl) amino-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) were prepared following six step starting 4-methoxy benzoic acid and using different secondary amines and were characterized with the help of FT-IR,(1)H,(13)C NMR, FAB Mass and nitrogen analysis...

WNK [with no lysine (k)] kinase is a serine/threonine kinase subfamily. Mutations in two of the WNK kinases result in pseudohypoaldosteronism type II (PHA II) characterized by hypertension, hyperkalemia, and metabolic acidosis. Recent studies showed that both WNK1 and WNK4 inhibit ROMK activity. However, little is known about the effect of WNK kinases on Maxi K, a large-conductance Ca(2+) and voltage-activated potassium (K) channel. Here, we report that WNK4 wild-type (WT) significantly inhibits Maxi K channel activity in HEK αBK stable cell lines compared with the control group...

Gating modifier peptides alter gating of voltage-gated potassium (KV) channels by binding to the voltage sensor paddle and changing the energetics of channel opening. Since the voltage sensor paddle is a modular motif with low sequence similarity across families, targeting of this region should yield highly specific channel modifiers. To test this idea, we developed a binding assay with the KV2.1 gating modifier, GxTX-1E. Monoiodotyrosine-GxTX-1E (125I-GxTX-1E) binds with high affinity (IC50 = 4 nM) to CHO cells stably expressing hKV2...

Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypomagnesemia, hypokalemic metabolic alkalosis, and hypocalciuria. To better model human GS caused by a specific mutation in the thiazide-sensitive Na(+) -Cl(-) cotransporter (NCC) gene SLC12A3, we generated a nonsense Ncc Ser707X knockin mouse corresponding to human p.Ser710X (c.2135C>A), a recurrent mutation with severe phenotypes in Chinese GS patients. Compared with wild-type or heterozygous littermates, homozygous (Hom) knockin mice fully recapitulated the phenotype of human GS...

BACKGROUND AND OBJECTIVE: A genetically diabetic mouse strain (db/db) exhibits severe obesity and a syndrome resembling human non-insulin-dependent diabetes mellitus. Our histological study of submandibular glands revealed that the size and area of the granular convoluted tubules was substantially decreased in db/db mice. We hypothesized that this structural difference reflected a specific alteration in salivary duct function. METHODS: The saliva evoked by pilocarpine was used for the measurement of ion concentrations, and submandibular glands were dissected out for the immunohistochemistry and real-time PCR study...

AIMS/HYPOTHESIS: The regulation of glucagon secretion from alpha cells is poorly understood. Since action potential firing at low glucose is required for glucagon secretion, we hypothesised that voltage-dependent K(+) (Kv) currents limit glucagon secretion under these conditions, similarly to their role in insulin secretion. METHODS: Kv currents and action potential firing of mouse and human alpha cells, identified by immunostaining, were examined by whole-cell patch-clamp...

The fine regulation of Na(+) and K(+) transport takes place in the cortical distal nephron. It is well established that K(+) secretion occurs through apical K(+) channels: the ROMK and the Ca(2+)- and voltage-dependent maxi-K. Previously, we identified the voltage-gated Kv1.3 channel in the inner medulla of the rat kidney (Escobar LI, Martínez-Téllez JC, Salas M, Castilla SA, Carrisoza R, Tapia D, Vázquez M, Bargas J, Bolívar JJ. Am J Physiol Cell Physiol 286: C965-C974, 2004). To examine the role of Kv1...

IMPORTANCE OF THE FIELD: Erectile dysfunction (ED) is the most common male sexual dysfunction presented for treatment affecting between 10 and 20% of men. PDE type 5 inhibitors (PDE5I) now account for the largest segment of the ED market. While these drugs are highly efficacious for many men, a relatively large subset of ED patients who do not respond to PDE5I is increasingly recognized. AREAS COVERED IN THIS REVIEW: In this review, we discuss clinical and preclinical evidence supporting various emerging compounds that regulate penile erection both centrally (clavulanic acid, dopamine and melanocortin receptor agonists) and peripherally (novel PDE5I, soluble and particulate guanylil cyclase activators, rho-kinase inhibitors and maxi-K channel openers)...

Background K(+) channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (glomus) cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and hypercapnia in TASK1- and/or TASK3-deficient mice have yielded conflicting results. We have characterized the glomus cell phenotype of TASK-null mice and studied the responses of individual cells to hypoxia and other chemical stimuli. CB morphology and glomus cell size were normal in wild-type as well as in TASK1(-/-) or double TASK1/3(-/-) mice...

In the past, many researchers considered viral vectors to be the most promising candidates to transfer genetic material into the corpora for the treatment of erectile dysfunction. However, at present, no viral vectors have progressed to human trials. In contrast, the use of naked gene therapy, a plasmid expressing the human Maxi-K potassium channel, is the only gene therapy treatment to be evaluated in clinical phase I trials to date. The success of these studies, proving the safety of this treatment, has paved the way for the development of future gene transfer techniques based on similar transfer methods, as well as novel treatment vectors, such as stem cell transfer...