Inward membrane current inChara inflata: II. Effects of pH, Cl−-channel blockers and NH 4 + , and significance for the hyperpolarized state

1986 ◽  
Vol 89 (2) ◽  
pp. 153-161 ◽  
Author(s):  
S. D. Tyerman ◽  
G. P. Findlay ◽  
G. J. Paterson
Keyword(s):  
Membrane Current ◽  
Channel Blockers ◽  
Cl Channel ◽  
Effects Of Ph

Epithelial modulation of afferent nerve endings: differential effects of amiloride on afferent subtypes

1995 ◽  
Vol 78 (6) ◽  
pp. 2235-2240 ◽  
Author(s):  
T. K. Ghosh ◽  
M. R. Van Scott ◽  
O. P. Mathew
Keyword(s):  
Superior Laryngeal Nerve ◽  
Nerve Endings ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Na Channels ◽  
Neural Signals ◽  
Cl Channel ◽  
Epithelial Na Channels ◽  
Afferent Nerve Endings ◽  
Cl Channels

Mechanisms underlying the differing chemosensitivity of laryngeal afferents have not been defined. The role of airway epithelium in transducing the chemical stimuli to neural signals was investigated by using Na(+)- and Cl(-)-channel inhibitors in anesthetized spontaneously breathing cats. Single-fiber action potentials were recorded from the peripheral cut end of the superior laryngeal nerve. Luminal application of amiloride (10(-4) M), an inhibitor of epithelial Na+ channels, reduced the responsiveness of non-respiratory-modulated endings (n = 25) to distilled water (65.76 +/- 5.77 vs. 50.67 +/- 5.13 Hz; P < 0.01). Water responsiveness of these endings was unaffected by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid and diphenylamine-2-carboxylate, two Cl(-)-channel blockers. Respiratory-modulated endings (water responsive, n = 8; water nonresponsive, n = 9) were unaffected by Na(+)- and Cl(-)-channel blockers. These results suggest that epithelial Na+ channels play a role in the modulation of non-respiratory-modulated laryngeal endings. The lack of an effect by amiloride on other subtypes may be due to differences in location or intrinsic properties of nerve endings. Cl- channels do not appear to play an important role in the modulation of laryngeal afferents targeted in this study.

Cl−-channel blockers in the thick ascending limb of the loop of Henle Structure activity relationship

1986 ◽  
Vol 407 (S2) ◽  
pp. S128-S141 ◽  
Author(s):  
P. Wangemann ◽  
M. Wittner ◽  
A. Di Stefano ◽  
H. C. Englert ◽  
H. J. Lang ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Channel Blockers ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Cl Channel ◽  
Structure Activity

Effects of pH on apical calcium entry and active calcium transport in rabbit cortical collecting system

1994 ◽  
Vol 266 (4) ◽  
pp. F620-F627 ◽  
Author(s):  
R. J. Bindels ◽  
A. Hartog ◽  
S. L. Abrahamse ◽  
C. H. Van Os
Keyword(s):  
Calcium Transport ◽  
Apical Membrane ◽  
Channel Blockers ◽  
Intracellular Acidification ◽  
Apical Side ◽  
Collecting Ducts ◽  
Effects Of Ph ◽  
Active Calcium ◽  
Permeable Supports ◽  
Collecting System

Rabbit connecting tubules and cortical collecting ducts were isolated by immunodissection and cultured on permeable supports. The monolayers actively transported Ca2+ with a net transcellular rate of 92 +/- 3 nmol.h-1.cm-2. Methoxyverapamil, felodipine, diltiazem, omega-conotoxin GVIA, and omega-agatoxin IVA when added to the apical side had no effect on Ca2+ absorption. Neither hyperpolarization nor depolarization of the apical membrane affected Ca2+ transport rates significantly. Stepwise lowering of the apical pH (pHa) from 8.0 to 5.6 gradually inhibited Ca2+ transport from 88 +/- 5 to 7 +/- 2 nmol.h-1.cm-2. Measuring the intracellular pH (pHi) with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein revealed that lowering the pHa from 8.0 to 5.6 decreased pHi from 7.8 to 6.7. To determine whether inhibition of Ca2+ absorption results from intracellular acidification, pHi was lowered using an NH4Cl pulse while extracellular pH was kept constant. Intracellular acidification from 7.4 +/- 0.2 to 6.9 +/- 0.1 reduced Ca2+ absorption by 26 +/- 6% only. In addition, lowering of the basolateral pH to 6.2 resulted in a pHi of 6.8 +/- 0.1, without affecting Ca2+ absorption rates. In conclusion, the basal Ca2+ influx mechanism in the apical membrane is most likely a voltage-independent Ca2+ transporter, insensitive to Ca2+ channel blockers, but strongly inhibited by apical acidification.

Colonic Cl channel blockade by three classes of compounds

1991 ◽  
Vol 261 (1) ◽  
pp. C51-C63 ◽  
Author(s):  
A. K. Singh ◽  
G. B. Afink ◽  
C. J. Venglarik ◽  
R. P. Wang ◽  
R. J. Bridges
Keyword(s):  
Open Channel ◽  
Single Channel ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Lipid Bilayer Membranes ◽  
Plasma Membrane Vesicles ◽  
Channel Protein ◽  
Cl Channel ◽  
Cytoplasmic Side ◽  
Potency Order

We compared the potency and inhibitory actions of three different classes of organic acids on a Cl channel derived from colonic enterocyte plasma membrane vesicles. Chloride channels were incorporated into planar lipid bilayer membranes to examine the effects of the anthranilic acids, diphenylamine 2-carboxylic acid (DPC) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), the indanyl alkanoic acids, 2-[(2-cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H-inden -5-yl)oxy] acetic acid (IAA-94) and its stereoenantiomer IAA-95, and the disulfonic stilbene, 4,4'-dinitro-stilbene-2,2'-disulfonic acid (DNDS). Except for DNDS, each of the blockers was equipotent from both the outer membrane and the cytoplasmic side of the channel protein. The potency order from the outmembrane side was DNDS greater than IAA-94 = IAA-95 greater than NPPB much greater than DPC. In contrast, the potency order from the cytoplasmic side was IAA-94 = IAA-95 greater than NPPB greater than DNDS much greater than DPC. DPC and NPPB caused a concentration-dependent decrease in the single-channel conductance (fast block). DNDS, IAA-94, and IAA-95 caused a flickery-type block and a concentration-dependent decrease in open-channel probability. Kinetic analysis revealed that blockade could be explained by a linear closed-opened-blocked kinetic scheme. Similarities in the electrostatic potential maps of these open-channel blockers suggest they may bind to a single shared binding site within the channel protein.

Interactions between intracellular Na+ levels and saxitoxin production in Cylindrospermopsis raciborskii T3

Microbiology ◽  
2004 ◽  
Vol 150 (2) ◽  
pp. 455-461 ◽  
Author(s):  
Francesco Pomati ◽  
Carlo Rossetti ◽  
Gianluca Manarolla ◽  
Brendan P. Burns ◽  
Brett A. Neilan
Keyword(s):  
Time Course ◽  
Paralytic Shellfish Poisoning ◽  
Cylindrospermopsis Raciborskii ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Shellfish Poisoning ◽  
Paralytic Shellfish ◽  
Channel Blocking ◽  
Effects Of Ph ◽  
Opposing Effects

Saxitoxin (STX) is the most potent representative among the paralytic shellfish poisoning (PSP) toxins, which are highly selective Na+ channel-blocking alkaloids. This study investigated, in cultures of the cyanobacterium Cylindrospermopsis raciborskii T3, the effects of pH, salt, amiloride and lidocaine hydrochloride on total cellular levels of Na+ and K+ ions and STX accumulation. Both Na+ levels and intracellular STX concentrations increased exponentially in response to rising alkalinity. NaCl inhibited cyanobacterial growth at a concentration of 10 mM. In comparison with osmotically stressed controls, however, NaCl promoted STX accumulation in a dose-dependent manner. A correlation was seen in the time-course of both total cellular Na+ levels and intracellular STX for NaCl, amiloride and lidocaine exposure. The increase in cellular Na+ induced by NaCl at 10 mM was coupled with a proportional accumulation of STX. The two Na+ channel-blocking agents amiloride and lidocaine had opposing effects on both cellular Na+ levels and STX accumulation. Amiloride at 1 mM reduced ion and toxin concentrations, while lidocaine at 1 μM increased the total cellular Na+ and STX levels. The effects of the channel-blockers were antagonistic and dependent on an alkaline pH. The results presented suggest that, in C. raciborskii T3, STX is responsive to cellular Na+ levels. This may indicate that either STX metabolism or the toxin itself could be linked to the maintenance of cyanobacterial homeostasis. The results also enhance the understanding of STX production and the ecology of PSP toxin-producing cyanobacteria.

Cl- channel blockers inhibit acid secretion in rabbit parietal cells

1990 ◽  
Vol 259 (4) ◽  
pp. G536-G543 ◽  
Author(s):  
D. H. Malinowska
Keyword(s):  
Atpase Activity ◽  
Acid Secretion ◽  
Transport Processes ◽  
Parietal Cells ◽  
Channel Blockers ◽  
Resting Cells ◽  
Inhibitory Effects ◽  
Intact Cells ◽  
Cl Channel ◽  
Cl Transport

Mechanisms of gastric parietal cell secretory membrane Cl- transport and the role of this Cl- transport in acid secretion were investigated by examining the effects of two Cl- channel blockers, diphenylamine-2-carboxylate (DPC) and 9-anthracene carboxylate (9-AC) on acid secretion using isolated, enriched rabbit parietal cells. Resting and stimulated acid secretion in intact cells (measured as [14C]aminopyrine accumulation) was inhibited by DPC and 9-AC, irrespective of agonist used. Apparent inhibition constants (Ki) were 2.4 x 10(-4) M for DPC and 1.2 x 10(-3) M for 9-AC for all responses. Digitonin-permeabilized parietal cells were used to bypass possible inhibitory effects of these compounds on basolateral membrane transport processes and to investigate effects only on the secretory membrane. Both blockers inhibited ATP-driven acid secretion in resting and stimulated permeable cells with apparent Ki values in the same range as measured in intact cells, suggesting that the site of action of these blockers is at the secretory membrane. H(+)-K(+)-ATPase activity in situ in permeable parietal cells, measured as 2-methyl-8-(phenylmethoxy)imidazo(1,2) pyridine-3-acetonitrile (SCH28080)-inhibitable ATP hydrolysis, was higher in stimulated compared with resting cells. Addition of 10 mM NH4Cl abolished this difference, and maximal H(+)-K(+)-ATPase activity was measured. SCH28080 and NH4Cl each abolished both resting and stimulated acid accumulation. DPC and 9-AC inhibited resting and stimulated H(+)-K(+)-ATPase activities, without exerting inhibitory effects on the enzyme itself, since the blockers had no effect on maximal NH4(+)-stimulated H(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of cell proliferation with induction of p21 by Cl− channel blockers in human leukemic cells

2004 ◽  
Vol 488 (1-3) ◽  
pp. 27-34 ◽  
Author(s):  
Baohong Jiang ◽  
Naoki Hattori ◽  
Bing Liu ◽  
Yasuhisa Nakayama ◽  
Kaori Kitagawa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Leukemic Cells ◽  
Channel Blockers ◽  
Cl Channel ◽  
Human Leukemic Cells

scholarly journals Effects of monocarboxylic acid-derived Cl−channel blockers on depolarization-activated potassium currents in rat ventricular myocytes

2007 ◽  
Vol 92 (3) ◽  
pp. 549-559 ◽  
Author(s):  
Shi-Sheng Zhou ◽  
Li-Bin Zhang ◽  
Wu-Ping Sun ◽  
Fu-Cheng Xiao ◽  
Yi-Ming Zhou ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Monocarboxylic Acid ◽  
Potassium Currents ◽  
Channel Blockers ◽  
Rat Ventricular Myocytes ◽  
Cl Channel

scholarly journals Calcium-activated chloride current amplifies the response to urine in mouse vomeronasal sensory neurons

2009 ◽  
Vol 135 (1) ◽  
pp. 3-13 ◽  
Author(s):  
Chun Yang ◽  
Rona J. Delay
Keyword(s):  
Sensory Neurons ◽  
Detection System ◽  
Reversal Potential ◽  
Vomeronasal Organ ◽  
Channel Blockers ◽  
Cl Channel ◽  
Chloride Accumulation ◽  
Perforated Patch Clamp ◽  
Whole Cell Recordings ◽  
Vomeronasal Sensory Neurons

The vomeronasal organ (VNO) is an odor detection system that mediates many pheromone-sensitive behaviors. Vomeronasal sensory neurons (VSNs), located in the VNO, are the initial site of interaction with odors/pheromones. However, how an individual VSN transduces chemical signals into electrical signals is still unresolved. Here, we show that a Ca2+-activated Cl− current contributes ∼80% of the response to urine in mouse VSNs. Using perforated patch clamp recordings with gramicidin, which leaves intracellular chloride undisrupted, we found that the urine-induced inward current (Vhold = −80 mV) was decreased in the presence of chloride channel blockers. This was confirmed using whole cell recordings and altering extracellular chloride to shift the reversal potential. Further, the urine-induced currents were eliminated when both extracellular Ca2+ and Na+ were removed. Using inside-out patches from dendritic tips, we recorded Ca2+-activated Cl− channel activity. Several candidates for this Ca2+-activated Cl− channel were detected in VNO by reverse transcription–polymerase chain reaction. In addition, a chloride cotransporter, Na+-K+-2Cl− isoform 1, was detected and found to mediate much of the chloride accumulation in VSNs. Collectively, our data demonstrate that chloride acts as a major amplifier for signal transduction in mouse VSNs. This amplification would increase the responsiveness to pheromones or odorants.

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