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.

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.

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.

Nasal Mucociliary Transport: New Evidence for a Key Role of Ciliary Beat Frequency

2002 ◽  
Vol 112 (3) ◽  
pp. 570-573 ◽  
Author(s):  
Wilbert M. Boek ◽  
Kees Graamans ◽  
Hanny Natzijl ◽  
Peter P. van Rijk ◽  
Egbert H. Huizing
Keyword(s):  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Mucociliary Transport ◽  
New Evidence ◽  
Ciliary Beat

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.

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.

Functional cross talk after activation of P2 and P1 receptors in oviductal ciliated cells

2000 ◽  
Vol 279 (3) ◽  
pp. C658-C669 ◽  
Author(s):  
Bernardo Morales ◽  
Nelson Barrera ◽  
Pablo Uribe ◽  
Claudio Mora ◽  
Manuel Villalón
Keyword(s):  
Cross Talk ◽  
Adenosine Receptors ◽  
Beat Frequency ◽  
Ciliated Cell ◽  
Ciliary Beat Frequency ◽  
Ciliary Activity ◽  
Dependent Manner ◽  
Ciliated Cells ◽  
P1 Receptors ◽  
Intracellular Ca

The presence of ATP and adenosine receptors and their role in controlling ciliary activity in oviductal ciliated cells was studied by measuring the ciliary beat frequency (CBF) in oviductal tissue cultures. ATP, adenosine, and related compounds increased the CBF in a dose-dependent manner. We established that P2 receptors of subtype 2Y2 and P1 receptors of subtype A2a mediated the responses to ATP and adenosine, respectively. We found evidence to suggest that stimulation of ciliary activity by ATP requires d- myo-inositol 1,4,5-trisphosphate [Ins(1,4,5) P 3] metabolism, intracellular Ca2+ mobilization, and protein kinase C activation. On the other hand, the adenosine effect is mediated by activation of a Gs protein-dependent pathway that enhances cAMP intracellular levels. To study the interaction between P2 and P1 receptors, cells were stimulated simultaneously with both agonists. We observed a synergistic increase of the CBF even at agonist concentrations (100 nM) that did not produce a significant response when added separately to the culture. Furthermore, a blocker of the cAMP pathway produced a reduction of the ATP response, whereas a blocker of the Ins(1,4,5) P 3 pathway also produced an inhibition of the adenosine response. Our evidence demonstrates that both ATP and adenosine receptors are present in a single ciliated cell and that a mechanism of cross talk could operate in the transduction pathways to control ciliary activity.

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 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.

scholarly journals Intracellular Cl− Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy

2020 ◽  
Vol 21 (11) ◽  
pp. 4052
Author(s):  
Makoto Yasuda ◽  
Taka-aki Inui ◽  
Shigeru Hirano ◽  
Shinji Asano ◽  
Tomonori Okazaki ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
High Speed ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Video Microscopy ◽  
Nasal Epithelial Cells ◽  
Ciliary Beating ◽  
High Speed Video ◽  
Human Nasal Epithelial Cells ◽  
Ciliary Beat

Small inhaled particles, which are entrapped by the mucous layer that is maintained by mucous secretion via mucin exocytosis and fluid secretion, are removed from the nasal cavity by beating cilia. The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca2+, H+ and Cl−), and is enhanced by a decreased concentration of intracellular Cl− ([Cl−]i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD, an index of ciliary beat amplitude) in cHNECs has been developed using high-speed video microscopy, which revealed that a decrease in [Cl−]i increased CBD, but not CBF, and an increase in [Cl−]i decreased both CBD and CBF. Thus, [Cl−]i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl− sensors and be regulated by [Cl−]i. These observations indicate that the activation of Cl− secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl−]i in cHNECs. Thus, [Cl−]i is critical for controlling ciliary beating in cHNECs. This review introduces the concept of Cl− regulation of ciliary beating in cHNECs.

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