scholarly journals Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the Platynereis larva

2017 ◽  
Author(s):  
Csaba Verasztó ◽  
Nobuo Ueda ◽  
Luis A. Bezares-Calderón ◽  
Aurora Panzera ◽  
Elizabeth A. Williams ◽  
...  
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Whole Body ◽  
Ciliary Activity ◽  
Ciliary Beating ◽  
Stop And Go ◽  
Multiciliated Cells ◽  
Platynereis Dumerilii ◽  
Catecholaminergic Cells ◽  
Ciliary Locomotion

AbstractCiliated surfaces harbouring synchronously beating cilia can generate fluid flow or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes in beat frequency are often coordinated across extended or discontinuous surfaces. To understand how such coordination is achieved, we studied the ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae have segmental multiciliated cells that regularly display spontaneous coordinated ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis, and neuron ablation to characterize the ciliomotor circuitry. We identified cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The synchronous rhythmic activation of cholinergic cells drives the coordinated arrests of all cilia. The serotonergic cells are active when cilia are beating. Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency. Based on their connectivity and alternating activity, the catecholaminergic cells may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go pacemaker system for the whole-body coordination of ciliary locomotion.

scholarly journals Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the Platynereis larva

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Csaba Verasztó ◽  
Nobuo Ueda ◽  
Luis A Bezares-Calderón ◽  
Aurora Panzera ◽  
Elizabeth A Williams ◽  
...  
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Whole Body ◽  
Ciliary Activity ◽  
Ciliary Beating ◽  
Stop And Go ◽  
Multiciliated Cells ◽  
Platynereis Dumerilii ◽  
Catecholaminergic Cells ◽  
Ciliary Locomotion

Ciliated surfaces harbouring synchronously beating cilia can generate fluid flow or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes in beat frequency are often coordinated across extended or discontinuous surfaces. To understand how such coordination is achieved, we studied the ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae have segmental multiciliated cells that regularly display spontaneous coordinated ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis, and neuron ablation to characterize the ciliomotor circuitry. We identified cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The synchronous rhythmic activation of cholinergic cells drives the coordinated arrests of all cilia. The serotonergic cells are active when cilia are beating. Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency. Based on their connectivity and alternating activity, the catecholaminergic cells may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go pacemaker system for the whole-body coordination of ciliary locomotion.

Differential effects of UTP, ATP, and adenosine on ciliary activity of human nasal epithelial cells

2001 ◽  
Vol 280 (6) ◽  
pp. C1485-C1497 ◽  
Author(s):  
Diane M. Morse ◽  
Jennifer L. Smullen ◽  
C. William Davis
Keyword(s):  
Epithelial Cells ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Maximal Effect ◽  
Ciliary Beating ◽  
Mediated Effects ◽  
Human Nasal Epithelium ◽  
Human Nasal Epithelial Cells ◽  
Sustained Responses

The purinergic regulation of ciliary activity was studied using small, continuously superfused explants of human nasal epithelium. The P2Y2 purinoceptor (P2Y2-R) was identified as the major purinoceptor regulating ciliary beat frequency (CBF); UTP (EC50 = 4.7 μM), ATP, and adenosine-5′- O-(3-thiotriphosphate) elicited similar maximal responses, approximately twofold over baseline. ATP, however, elicited a post-peak sustained plateau in CBF (1.83 ± 0.1-fold), whereas the post-peak CBF response to UTP declined over 15 min to a low-level plateau (1.36 ± 0.16-fold). UDP also stimulated ciliary beating, probably via P2Y6-R, with a maximal effect approximately one-half that elicited by P2Y2-R stimulation. Not indicated were P2Y1-R-, P2Y4-R-, or P2Y11-R-mediated effects. A2B-receptor agonists elicited sustained responses in CBF approximately equal to those from UTP/ATP [5′-( N-ethylcarboxamido)adenosine, EC50 = 0.09 μM; adenosine, EC50 = 0.7 μM]. Surprisingly, ADP elicited a sustained stimulation in CBF. The ADP effect and the post-peak sustained portion of the ATP response in CBF were inhibited by the A2-R antagonist 8-( p-sulfophenyl)theophylline. Hence, ATP affects ciliary activity through P2Y2-R and, after an apparent ectohydrolysis to adenosine, through A2BAR.

Effect of pH, Viscosity and Ionic-Strength Changes on Ciliary Beating Frequency of Human Bronchial Explants

1983 ◽  
Vol 64 (4) ◽  
pp. 449-451 ◽  
Author(s):  
Chun Ka Luk ◽  
Mauricio J. Dulfano
Keyword(s):  
Ionic Strength ◽  
Marked Reduction ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Rapid Loss ◽  
Significant Drop ◽  
Ciliary Beating ◽  
Beating Frequency

1. Ciliary activity is significantly influenced by chemical and physical properties of the liquid medium in which the cilia beat. 2. We studied the effect of changes in pH, ionic strength and viscosity on the ciliary beat frequency (CBF) of explants of human respiratory mucosa. 3. Optimal CBF was elicited at pH 7.0-9.0, with a marked reduction of CBF outside these limits. The CBF was well preserved at NaCl concentrations between 5 g/l (80 mmol/l) and 12 g/l (200 mmol/l), but there was rapid loss at concentrations below 0.5 gA (10 mmol/l). The cilia beat best at viscosities below 1.0 centipoises (1 mN s m−2). Increase of the viscosity gradually decreases CBF with a significant drop at viscosities above 87 millipoises. 4. It is concluded that the above limits may fairly accurately indicate the actual physical characteristics of the periciliary environment (‘sol layer’) in vivo.

scholarly journals nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea

2021 ◽  
Vol 4 (5) ◽  
pp. e202000981
Author(s):  
Anatoly Mikhailik ◽  
Tatyana V Michurina ◽  
Krikor Dikranian ◽  
Stephen Hearn ◽  
Vladimir I Maxakov ◽  
...  
Keyword(s):  
Beat Frequency ◽  
Ciliated Cell ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Ciliated Cells ◽  
No Donors ◽  
Multiciliated Cells ◽  
Human Disorders ◽  
Low Levels ◽  
Ciliary Beat

Clearance of the airway is dependent on directional mucus flow across the mucociliary epithelium, and deficient flow is implicated in a range of human disorders. Efficient flow relies on proper polarization of the multiciliated cells and sufficient ciliary beat frequency. We show that NO, produced by nNOS in the multiciliated cells of the mouse trachea, controls both the planar polarity and the ciliary beat frequency and is thereby necessary for the generation of the robust flow. The effect of nNOS on the polarity of ciliated cells relies on its interactions with the apical networks of actin and microtubules and involves RhoA activation. The action of nNOS on the beat frequency is mediated by guanylate cyclase; both NO donors and cGMP can augment fluid flow in the trachea and rescue the deficient flow in nNOS mutants. Our results link insufficient availability of NO in ciliated cells to defects in flow and ciliary activity and may thereby explain the low levels of exhaled NO in ciliopathies.

scholarly journals PKA induces Ca2+ release and enhances ciliary beat frequency in a Ca2+-dependent and -independent manner

1998 ◽  
Vol 275 (3) ◽  
pp. C790-C797 ◽  
Author(s):  
Alex Braiman ◽  
Orna Zagoory ◽  
Zvi Priel
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Experimental Conditions ◽  
Independent Manner ◽  
Ciliary Beating ◽  
Independent Mechanism ◽  
Intracellular Ca ◽  
Ciliary Beat

The intent of this work was to evaluate the role of cAMP in regulation of ciliary activity in frog mucociliary epithelium and to examine the possibility of cross talk between the cAMP- and Ca2+-dependent pathways in that regulation. Forskolin and dibutyryl cAMP induced strong transient intracellular Ca2+ concentration ([Ca2+]i) elevation and strong ciliary beat frequency enhancement with prolonged stabilization at an elevated plateau. The response was not affected by reduction of extracellular Ca2+concentration. The elevation in [Ca2+]iwas canceled by pretreatment with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM, thapsigargin, and a phospholipase C inhibitor, U-73122. Under those experimental conditions, forskolin raised the beat frequency to a moderately elevated plateau, whereas the initial strong rise in frequency was completely abolished. All effects were canceled by H-89, a selective protein kinase A (PKA) inhibitor. The results suggest a dual role for PKA in ciliary regulation. PKA releases Ca2+ from intracellular stores, strongly activating ciliary beating, and, concurrently, produces moderate prolonged enhancement of the beat frequency by a Ca2+-independent mechanism.

scholarly journals Distinct Axonemal Processes Underlie Spontaneous and Stimulated Airway Ciliary Activity

2002 ◽  
Vol 120 (6) ◽  
pp. 875-885 ◽  
Author(s):  
Weiyuan Ma ◽  
Shai D. Silberberg ◽  
Zvi Priel
Keyword(s):  
Cyclic Nucleotides ◽  
Molecular Mechanisms ◽  
Beat Frequency ◽  
Physiological Mechanism ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Biological Transport ◽  
Patch Clamp Technique ◽  
Ciliary Beating ◽  
Intense Research

Cilia are small organelles protruding from the cell surface that beat synchronously, producing biological transport. Despite intense research for over a century, the mechanisms underlying ciliary beating are still not well understood. Even the nature of the cytosolic molecules required for spontaneous and stimulated beating is debatable. In an effort to resolve fundamental questions related to cilia beating, we developed a method that integrates the whole-cell mode of the patch-clamp technique with ciliary beat frequency measurements on a single cell. This method enables to control the composition of the intracellular solution while the cilia remain intact, thus providing a unique tool to simultaneously investigate the biochemical and physiological mechanism of ciliary beating. Thus far, we investigated whether the spontaneous and stimulated states of cilia beating are controlled by the same intracellular molecular mechanisms. It was found that: (a) MgATP was sufficient to support spontaneous beating. (b) Ca2+ alone or Ca2+-calmodulin at concentrations as high as 1 μM could not alter ciliary beating. (c) In the absence of Ca2+, cyclic nucleotides produced a moderate rise in ciliary beating while in the presence of Ca2+ robust enhancement was observed. These results suggest that the axonemal machinery can function in at least two different modes.

Effects of ethanol on in vitro ciliary motility

1988 ◽  
Vol 65 (4) ◽  
pp. 1617-1620 ◽  
Author(s):  
D. R. Maurer ◽  
J. Liebman
Keyword(s):  
Beat Frequency ◽  
Slow Motion ◽  
Ciliary Beat Frequency ◽  
Blood Levels ◽  
Ciliary Beating ◽  
Ciliary Motility ◽  
Social Drinking ◽  
High Concentrations ◽  
Ciliary Beat

Consumption of ethanol can impair lung function and slow total lung clearance. High concentrations of ethanol have been shown to slow or arrest ciliary beating. This study examined the effects of concentrations of alcohol comparable to blood levels achieved from social drinking on ciliary beat frequency. We obtained ciliated cells by brushing the trachea of unanesthetized sheep during fiber-optic bronchoscopy. The cells were suspended in a perfusion chamber and physiological conditions were maintained in vitro. Ciliary beat frequency and synchrony were determined by slow-motion analysis of video images obtained by interference contrast microscopy. Metachronal ciliary coordination was observed in all preparations. The ciliary beat frequency was stimulated at ethanol concentrations from 0.01 up to but not including 0.1%, unchanged at 0.5 and 1%, and slowed at 2%. While confirming inhibition of ciliary motility at very high ethanol levels, we observed no acute impairment of ciliary function at ethanol concentrations comparable to those achieved from social drinking. Indeed, we found an unexpected stimulation of ciliary beating at low levels of ethanol. How this alteration in ciliary beating would affect pulmonary clearance remains unknown at this time.

scholarly journals Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia

2019 ◽  
Vol 57 (4) ◽  
pp. 237-244 ◽  
Author(s):  
Sylvain Blanchon ◽  
Marie Legendre ◽  
Mathieu Bottier ◽  
Aline Tamalet ◽  
Guy Montantin ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
High Speed ◽  
Genetic Disorder ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Central Complex ◽  
Ciliary Beating ◽  
Recovery Stroke ◽  
Biallelic Mutations ◽  
Ciliary Dyskinesia

BackgroundPrimary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.MethodsWe prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).ResultsSixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.ConclusionQuantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.

Altered Sinonasal Ciliary Dynamics in Chronic Rhinosinusitis

2006 ◽  
Vol 20 (3) ◽  
pp. 325-329 ◽  
Author(s):  
Bei Chen ◽  
Jeffrey Shaari ◽  
Steven Eau Claire ◽  
James N. Palmer ◽  
Alexander G. Chiu ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Adenosine Triphosphate ◽  
High Speed ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Differential Interference Contrast Microscopy ◽  
Dynamic Regulation ◽  
Mucus Clearance ◽  
Persistent Inflammation

Background Although multiple etiologies contribute to the development of rhinosinusitis, a common pathophysiological sequelae is ineffective sinonasal mucociliary clearance, resulting in stasis of sinonasal secretions, with subsequent infection, and persistent inflammation. The respiratory cilia beat continually at a basal rate, while during times of stress, such as exercise or infection, ciliary beat frequency (CBF) increases, accelerating mucus clearance. Previous investigations have led to conflicting results with some authors reporting decreased CBF while others have found normal values of CBF in patients with chronic rhinosinusitis (CRS). Additionally, these studies have only analyzed basal CBF. The goal of this study was to compare the basal as well as the stimulated sinonasal CBF in patients with CRS versus controls. Methods A dual temperature controlled perfusion chamber, differential interference contrast microscopy, and high-speed digital video were used to analyze both basal and adenosine triphosphate (100 μM)–stimulated CBF in human sinonasal mucosal explants. Results Although no difference in basal CBF was detected between control and CRS patients, a marked difference in stimulated CBF was noted. Exogenously applied adenosine triphosphate resulted in a 50–70% increase of CBF in control tissue with a minimally observed CBF increase in explants from CRS patients. Conclusion Dynamic regulation of respiratory ciliary activity is critical for the respiratory epithelium to adapt to varying environmental situations. Thus, diminished or absent adaptation could predispose the sinonasal cavity to accumulation of inhaled infectious and noxious particulate matter resulting in infection/inflammation. Our findings suggest that CRS patients have decreased sinonasal ciliary adaptation to environmental stimuli.

Honorable Mention — Student Research Award 1995: Signal Transduction Mechanisms in Substance P-Mediated Ciliostimulation

1995 ◽  
Vol 113 (5) ◽  
pp. 582-588 ◽  
Author(s):  
Rodney J. Schlosser ◽  
Judith M. Czaja ◽  
Thomas V. McCaffrey
Keyword(s):  
Nitric Oxide ◽  
Substance P ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Intermediate Step ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Vitro Effect ◽  
Ciliary Beat

Substance P is a neuropeptide released by afferent neurons in the respiratory tract during inflammatory reactions. It produces effects on blood vessels, bronchial smooth muscle, nasal glands, and respiratory cilia. We studied the in vitro effect of substance P on the ciliary beat frequency of human adenoid explants and its mechanism of action. Substance P was added to cultured adenoid at concentrations of 10−10, 10−8, 10−6, and 10−4 mol/L. Ciliary beat frequency was determined with phase-contrast microscopy and microphotometry. Substance P increased ciliary beat frequency a maximum of 11.9% ± 3.8% ( p < 0.01). Diclofenac (10−6 mol/L) significantly blocked the ciliostimulatory effects of SP ( p < 0.022), indicating that prostaglandin synthesis is an intermediate step in the action of substance P on ciliary beat frequency. The L-arginine analogs, NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, inhibit nitric oxide synthesis from L-arginine. L-Arginine analogs (10−4 to 10−2 mol/L) inhibited the effect of substance P ( p < 0.02 at the higher concentration). This inhibition was reversed by adding L-arginine, demonstrating that nitric oxide production is a required step in substance P-induced ciliostimulation. Substance P stimulates ciliary activity in human nasal mucosa as a result of secondary production and release of endogenous prostaglandins and nitric oxide. It is likely that inflammatory disease processes that stimulate release of substance P and subsequent prostaglandin and nitric oxide production modify mucociliary transport. Pharmacologic modification of substance P and its second messengers may eventually permit regulation of this important defense mechanism and control of neurogenic inflammation.

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