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

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.

2001 ◽  
Vol 280 (6) ◽  
pp. C1485-C1497 ◽  
Author(s):  
Diane M. Morse ◽  
Jennifer L. Smullen ◽  
C. William Davis

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.


2017 ◽  
Author(s):  
Csaba Verasztó ◽  
Nobuo Ueda ◽  
Luis A. Bezares-Calderón ◽  
Aurora Panzera ◽  
Elizabeth A. Williams ◽  
...  

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.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Csaba Verasztó ◽  
Nobuo Ueda ◽  
Luis A Bezares-Calderón ◽  
Aurora Panzera ◽  
Elizabeth A Williams ◽  
...  

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.


1998 ◽  
Vol 275 (3) ◽  
pp. C790-C797 ◽  
Author(s):  
Alex Braiman ◽  
Orna Zagoory ◽  
Zvi Priel

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.


1988 ◽  
Vol 65 (2) ◽  
pp. 971-981 ◽  
Author(s):  
L. B. Wong ◽  
I. F. Miller ◽  
D. B. Yeates

beta 2-Adrenergic bronchodilator and muscarinic cholinergic bronchoconstrictor agonists both stimulate ciliary activity in vitro. To test the hypothesis that increases in autonomic activity would result in increases in ciliary beat frequency (CBF) in vivo, a correlation analysis heterodyne laser light-scattering system was developed and validated to measure the stimulating effects of sympathomimetic and parasympathomimetic agonists on tracheal CBF in intact, anesthetized beagles. The mean baseline CBF from 42 studies of 274 measurements in 9 (5 male and 4 female) adult beagles was 6.6 +/- 1.1 Hz. The stimulating effects of a beta 2-adrenergic agonist, fenoterol, and a muscarinic cholinergic agonist, methacholine, on CBF were studied on four and eight beagles, respectively. The studies were randomized and blinded. Aerosolized 10(-5) M fenoterol stimulated the CBF from the base line of 6.8 +/- 2.5 to 32.0 +/- 17.9 Hz in four dogs. Aerosolized methacholine stimulated the CBF from the base line of 5.8 +/- 0.7 to 9.4 +/- 3.0 Hz for 10(-8) M, and to 12.6 +/- 3.1 Hz for 10(-6) M in eight dogs. These are the first data obtained in intact animals that demonstrate CBF in the lower respiratory tract is regulated by autonomic agonists.


1982 ◽  
Vol 52 (4) ◽  
pp. 1018-1023 ◽  
Author(s):  
D. R. Maurer ◽  
M. Sielczak ◽  
W. Oliver ◽  
W. M. Abraham ◽  
A. Wanner

The purpose of this investigation was to determine if abnormal ciliary function contributes to allergic mucociliary dysfunction. In conscious sheep with Ascaris suum hypersensitivity, ciliated cells were obtained with a cytology brush and tracheal mucous velocity (TMV) was determined before and serially for 2 h following antigen inhalation. The recovered cells (also containing mast cells) were suspended in a chamber, and ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of ciliary beat frequency (CBF). One hour after A. suum challenge mean CBF (+/- SE) showed a slight increase from a base-line value of 630 +/- 16 to 716 +/- 30 beats/min (P less than 0.05) when mean TMV was decreased to 57% of base line (P less than 0.05). After 2 h, both mean CBF and TMV returned toward base line. Since possible in vivo actions of chemical mediators liberated by antigen challenge may have been lost after suspension of the brushed cells, we also assessed the effects of antigen on CBF in vitro. A. suum caused a dose-dependent increase in CBF that was blocked by cromolyn sodium. We conclude that 1) allergic mucociliary dysfunction is not caused by a decrease in CBF and 2) antigen-induced release of chemical mediators increases CBF.


2002 ◽  
Vol 120 (6) ◽  
pp. 875-885 ◽  
Author(s):  
Weiyuan Ma ◽  
Shai D. Silberberg ◽  
Zvi Priel

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.


1995 ◽  
Vol 104 (10) ◽  
pp. 798-802 ◽  
Author(s):  
Paul J. Schuil ◽  
Maartje Ten Berge ◽  
Kees Graamans ◽  
José M. E. Van Gelder ◽  
Egbert H. Huizing

On stimulation of trigeminal nerve endings, neuropeptides are released into the nasal mucosa. Among these neuropeptides is substance P (SP). In this study, we determined the effect in vitro of SP, as well as SP together with thiorphan, a blocker of the SP-degrading enzyme neutral endopeptidase, on the ciliary beat frequency (CBF) of the human upper respiratory tract. Ciliated epithelium of human adenoid tissue was used in the experiments. The CBF was measured by means of a computer-assisted photoelectric method. Substance P (10−8 to 10−5 mol/L, n = 7) showed a small but statistically significant dose-dependent decrease in CBF. On perfusion with SP (10−8 to 10−5 mol/L, n = 8) in combination with thiorphan, no statistically significant effect was found. We conclude that SP does not have a direct effect on ciliary activity to such an extent that it will affect mucociliary transport in vivo.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyle S. Feldman ◽  
Eunwon Kim ◽  
Michael J. Czachowski ◽  
Yijen Wu ◽  
Cecilia W. Lo ◽  
...  

AbstractRespiratory mucociliary clearance (MCC) is a key defense mechanism that functions to entrap and transport inhaled pollutants, particulates, and pathogens away from the lungs. Previous work has identified a number of anesthetics to have cilia depressive effects in vitro. Wild-type C57BL/6 J mice received intra-tracheal installation of 99mTc-Sulfur colloid, and were imaged using a dual-modality SPECT/CT system at 0 and 6 h to measure baseline MCC (n = 8). Mice were challenged for one hour with inhalational 1.5% isoflurane, or intraperitoneal ketamine (100 mg/kg)/xylazine (20 mg/kg), ketamine (0.5 mg/kg)/dexmedetomidine (50 mg/kg), fentanyl (0.2 mg/kg)/1.5% isoflurane, propofol (120 mg/Kg), or fentanyl/midazolam/dexmedetomidine (0.025 mg/kg/2.5 mg/kg/0.25 mg/kg) prior to MCC assessment. The baseline MCC was 6.4%, and was significantly reduced to 3.7% (p = 0.04) and 3.0% (p = 0.01) by ketamine/xylazine and ketamine/dexmedetomidine challenge respectively. Importantly, combinations of drugs containing fentanyl, and propofol in isolation did not significantly depress MCC. Although no change in cilia length or percent ciliation was expected, we tried to correlate ex-vivo tracheal cilia ciliary beat frequency and cilia-generated flow velocities with MCC and found no correlation. Our results indicate that anesthetics containing ketamine (ketamine/xylazine and ketamine/dexmedetomidine) significantly depress MCC, while combinations containing fentanyl (fentanyl/isoflurane, fentanyl/midazolam/dexmedetomidine) and propofol do not. Our method for assessing MCC is reproducible and has utility for studying the effects of other drug combinations.


1998 ◽  
Vol 12 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Mark Jorissen

Mucociliary transport is one of the most important defense mechanisms of the airway. Mucociliary transport time or rate, as measured using the saccharin test or the radioisotope technique, respectively, is clinically the most relevant parameter, although subject to large intra- and interindividual variability. There is no correlation between mucociliary transport in vivo and ciliary beat frequency ex vivo. Preliminary evidence demonstrates that mucociliary transport correlates with ciliary structure and orientation as investigated with transmission and scanning electron microscopy. A correlation is presented between ciliary beat frequency and secondary ciliary abnormalities. This correlation can best be described according to the logistic sigmoid model (r = 0.69). Based on these functional data, an ultrastructural distinction is proposed among normal (less than 5%), light (5 to 15%), moderate (15 to 25%), and severe (more than 25%) secondary ciliary dyskinesia.


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