Opposing roles of K<sup>+</sup>and Cl<sup>−</sup>channels in maintenance of opossum lower esophageal sphincter tone

Zhang, Yong; Miller, David V.; Paterson, William G.

doi:10.1152/ajpgi.2000.279.6.g1226

Cited by 35 publications

(39 citation statements)

References 45 publications

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“…We speculate that in circular smooth muscle of the opossum LES, the activation of K Na channels may serve to stabilize the RMP. The basal tone of the LES is maintained by constant Ca ϩ influx via ongoing Ca 2ϩ action potentials (34), and the accumulated Ca 2ϩ is likely extruded from the cell via a Na ϩ /Ca 2ϩ exchanger (25). This, in turn, leads to the accumulation of intracellular Na ϩ that should activate K Na channels, thereby counterbalancing the alteration of membrane potential produced by activity of the Na ϩ /Ca 2ϩ pump.…”

Section: Discussionmentioning

confidence: 99%

Functional evidence for Na⁺-activated K⁺ channels in circular smooth muscle of the opossum lower esophageal sphincter

Zhang

Paterson²

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Na+ reduction induces contraction of opossum lower esophageal sphincter (LES) circular smooth muscle strips in vitro; however, the mechanism(s) by which this occurs is unknown. The purpose of the present study was to investigate the electrophysiological effects of low Na+ on opossum LES circular smooth muscle. In the presence of atropine, quanethidine, nifedipine, and substance P, conventional intracellular electrodes recorded a resting membrane potential (RMP) of −37.5 ± 0.9 mV ( n = 4). Decreasing [Na+] from 144.1 to 26.1 mM by substitution of equimolar NaCl with choline Cl depolarized the RMP by 7.1 ± 1.1 mV. Whole cell patch-clamp recordings revealed outward K+ currents that began to activate at −60 mV using 400-ms stepped test pulses (−120 to +100 mV) with increments of 20 mV from holding potential of −80 mV. Reduction of [Na+] in the bath solution inhibited K+ currents in a concentration-dependent manner. Single channels with conductance of 49–60 pS were recorded using cell-attached patch-clamp configurations. The channel open probability was significantly decreased by substitution of bath Na+ with equimolar choline. A 10-fold increase of [K+] in the pipette shifted the reversal potential of the single channels to the positive by −50 mV. These data suggest that Na+-activated K+ channels exist in the circular smooth muscle of the opossum LES.

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Section: Discussionmentioning

confidence: 99%

Functional evidence for Na⁺-activated K⁺ channels in circular smooth muscle of the opossum lower esophageal sphincter

Zhang

Paterson²

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…More recently, a role for Ca 2ϩ influx via L-type Ca 2ϩ channels was demonstrated in several animal models, including canine (Salapatek et al, 1998), feline (Muinuddin et al, 2004), and opossum (Zhang et al, 2000) LES. Our previous studies in human esophagus at both the tissue and cell levels revealed similar dependence on extracellular Ca 2ϩ (Kovac et al, 2005).…”

Section: Downloaded Frommentioning

confidence: 99%

Calcium Sensitization in Human Esophageal Muscle: Role for RhoA Kinase in Maintenance of Lower Esophageal Sphincter Tone

Sims

Chrones²,

Preiksaitis³

2008

J Pharmacol Exp Ther

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A rise in intracellular-free calcium ([Ca 2ϩ ] i ) concentration is important for initiating contraction of smooth muscles, and Ca 2ϩ sensitization involving RhoA kinase can sustain tension. We previously found that [Ca 2ϩ ] i was comparable in cells from the esophageal body (EB) and lower esophageal sphincter (LES) muscles, despite the fact that the LES maintains resting tone. We hypothesized that Ca 2ϩ sensitization contributes to contraction in human esophageal muscle. Tension and [Ca 2ϩ ] i were measured simultaneously in intact human EB and LES muscles using the ratiometric Ca Protein kinase C inhibitors reduced force to a lesser extent. RhoA-kinase blockers caused concentration-dependent reduction of tension in spontaneously contracted LES muscles. Moreover, RhoA-kinase blockers reduced intrinsic nerve-evoked and carbacholevoked contraction. However, there was no effect on nerve-or nitric oxide-mediated relaxation of LES. Ca 2ϩ sensitization mediated by the RhoA-kinase pathway has an important role in contraction of human EB muscles and LES tonic contraction, a feature not previously recognized.

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“…These channels also participate in spontaneous contractions of smooth muscle in lower esophageal sphincter and myometrium [8,9]. In addition, Ca 2+ -activated Cl -channels, which are expressed in many cell types, are involved in signal transduction for diverse physiological functions such as membrane excitability, osmotic balance, transepithelial chloride movements, or fluid secretion [10].…”

Section: Introductionmentioning

confidence: 99%

Role of Chloride Channels in the Regulation of Corpus Cavernosum Tone: A Potential Therapeutic Target for Erectile Dysfunction

Chu

Adaikan

2008

The Journal of Sexual Medicine

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Introduction Recent electrophysiological recordings have identified the existence of outward, excitatory chloride (Cl−) currents in rat, rabbit, and human corpus cavernosum (CC) muscle cells. Aim The aim of this study was to investigate the physiological role of Cl− currents in the maintenance of cavernosal muscle tone in isolated rabbit CC tissues. Methods CC strips (1 × 1 × 5 mm) were suspended in tissue bath chambers for isometric tension experiments. Spontaneous cavernosal tone and contractions elicited by field stimulation or administration of established smooth muscle constrictors were examined in the presence of chloride channel (ClC) blockers, ni umic acid (NFA), and anthracene-9-carboxylic acid (A9C). Main Outcome Measure Both spontaneous myogenic activity and contractile responses to field stimulation, norepinephrine, histamine, and endothelin-1 were reduced by ClC blockers. Results In CC strips exhibiting intrinsic myogenic tone, NFA (30 and 100 µM) and A9C (1 mM) caused a relaxation of the tone. In addition, spontaneous contractile activity in CC was abolished in the presence of either ClC blocker. In CC strips precontracted with norepinephrine, histamine, and endothelin-1, both ClC blockers significantly reversed the tone. The ability of NFA and A9C to reverse norepinephrine-induced tone was unaffected by N ω-nitro-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine. In addition, neither indomethacin nor tetraethylammonium affected the relaxant response of NFA. NFA and A9C inhibited the neurogenic and norepinephrine-induced contractions in a concentration-dependent manner. While NFA exerted persistent inhibition on neurogenic contraction, inhibition of neurogenic contractions by A9C was readily reversible. On K+-depolarized CC, NFA induced a concentration-related relaxation, whereas A9C was inert, suggesting an additional mechanism of NFA on voltage-gated calcium channels. Conclusions These results underline the importance of Cl− currents as a mechanism in the maintenance of cavernosal tone produced by adrenergic and various endogenous constrictors. Thus, the modulation of Cl− current, as an attractive and effective approach to regulate penile erection, and specific ClC blockers, as potential erectogenic agents, merits further research.

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Opposing roles of K⁺and Cl⁻channels in maintenance of opossum lower esophageal sphincter tone

Cited by 35 publications

References 45 publications

Functional evidence for Na⁺-activated K⁺ channels in circular smooth muscle of the opossum lower esophageal sphincter

Functional evidence for Na⁺-activated K⁺ channels in circular smooth muscle of the opossum lower esophageal sphincter

Calcium Sensitization in Human Esophageal Muscle: Role for RhoA Kinase in Maintenance of Lower Esophageal Sphincter Tone

Role of Chloride Channels in the Regulation of Corpus Cavernosum Tone: A Potential Therapeutic Target for Erectile Dysfunction

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Opposing roles of K+and Cl−channels in maintenance of opossum lower esophageal sphincter tone

Cited by 35 publications

References 45 publications

Functional evidence for Na+-activated K+ channels in circular smooth muscle of the opossum lower esophageal sphincter

Functional evidence for Na+-activated K+ channels in circular smooth muscle of the opossum lower esophageal sphincter

Calcium Sensitization in Human Esophageal Muscle: Role for RhoA Kinase in Maintenance of Lower Esophageal Sphincter Tone

Role of Chloride Channels in the Regulation of Corpus Cavernosum Tone: A Potential Therapeutic Target for Erectile Dysfunction

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Opposing roles of K⁺and Cl⁻channels in maintenance of opossum lower esophageal sphincter tone

Functional evidence for Na⁺-activated K⁺ channels in circular smooth muscle of the opossum lower esophageal sphincter

Functional evidence for Na⁺-activated K⁺ channels in circular smooth muscle of the opossum lower esophageal sphincter