Control of the beat cycle of respiratory tract cilia by Ca2+ and cAMP

Department of Anatomy and Cell Biology, University of California School of Medicine, Los Angeles 90024.
The American journal of physiology (Impact Factor: 3.28). 09/1992; 263(2 Pt 1):L232-42.
Source: PubMed


Beat frequency and the duration of the constituent recovery, effective, and rest phases of the beat cycle of respiratory tract cilia were measured photoelectronically before and after manipulation with ionomycin or isoproterenol. Both ionomycin, acting by increasing intracellular Ca2+, and isoproterenol, acting by elevating intracellular adenosine 3',5'-cyclic monophosphate (cAMP), increased beat frequency by reducing the duration of the three phases of the ciliary beat cycle in a similar manner. The addition of increasing concentrations of ATP to ciliated cells permeabilized by exposure to saponin caused a pattern of phase reduction indistinguishable from that observed in whole cells. The beat frequency of permeabilized cells was slower than that of whole cells and insensitive to changes in Ca2+ and cAMP. Ca2+ and cAMP may regulate ciliary beat frequency by acting at a common site within intact cells, possibly regulating the rate at which the axoneme can use ATP or the availability of ATP to the axoneme.

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    • ") but is periodic with a frequency of typically 5 Hz at room temperature and 10 Hz at 37°C for healthy airway epithelium [36]. The speckle pattern in OCT arises from interferences between sub-resolution light scatterers, such as cilia. "
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    ABSTRACT: Muco-ciliary transport in the human airway is a crucial defense mechanism for removing inhaled pathogens. Optical coherence tomography (OCT) is well-suited to monitor functional dynamics of cilia and mucus on the airway epithelium. Here we demonstrate several OCT-based methods upon an actively transporting in vitro bronchial epithelial model and ex vivo mouse trachea. We show quantitative flow imaging of optically turbid mucus, semi-quantitative analysis of the ciliary beat frequency, and functional imaging of the periciliary layer. These may translate to clinical methods for endoscopic monitoring of muco-ciliary transport in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD).
    Biomedical Optics Express 09/2012; 3(9):1978-92. DOI:10.1364/BOE.3.001978 · 3.65 Impact Factor
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    • "These observations highlighted the role of intracellular Ca 2+ and of CaCC conductance in CF physiopathology. Moreover , it has been well established that airway ciliary beat frequency (CBF) is strongly regulated by second messenger, such as Ca 2+ (Lansley et al., 1992; Braiman et al., 1998; Evans and Sanderson, 1999). The CBF is a key factor for the regulation of mucociliary transport and thus for the mechanisms of defense of the respiratory tract (Satir and Sleigh, 1990; Wanner et al., 1996). "
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    ABSTRACT: Among the diverse physiological functions exerted by calcium signaling in living cells, its role in the regulation of protein biogenesis and trafficking remains incompletely understood. In cystic fibrosis (CF) disease the most common CF transmembrane conductance regulator (CFTR) mutation, F508del-CFTR generates a misprocessed protein that is abnormally retained in the endoplasmic reticulum (ER) compartment, rapidly degraded by the ubiquitin/proteasome pathway and hence absent at the plasma membrane of CF epithelial cells. Recent studies have demonstrated that intracellular calcium signals consequent to activation of apical G-protein-coupled receptors by different agonists are increased in CF airway epithelia. Moreover, the regulation of various intracellular calcium storage compartments, such as ER is also abnormal in CF cells. Although the molecular mechanism at the origin of this increase remains puzzling in epithelial cells, the F508del-CFTR mutation is proposed to be the onset of abnormal Ca(2+) influx linking the calcium signaling to CFTR pathobiology. This article reviews the relationships between CFTR and calcium signaling in the context of the genetic disease CF.
    Frontiers in Pharmacology 10/2011; 2:67. DOI:10.3389/fphar.2011.00067 · 3.80 Impact Factor
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    • "One of the possible outcomes of Ca–CaM complex formation is activation of the cAMP-dependent pathway via Ca–CaM sensitive adenylate cyclases [37]. Along with Ca 2+ , this pathway has been identified as an important element of CBF regulation [3] [14] [16] [38] [39]. Indeed, we show here that PKA inhibitors block NH 4 Cl-induced CBF enhancement (Fig. 8). "
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    ABSTRACT: Using confocal microscopy we demonstrate that ciliary cells from airway epithelium maintain two qualitatively distinct cytosolic regions in terms of pH regulation. While the bulk of the cytosol is stringently buffered and is virtually insensitive to changes in extracellular pH (pHo), the values of cytosolic pH in the vicinity of the ciliary membrane is largely determined by pHo. Variation of pHo from 6.2 up to 8.5 failed to affect ciliary beat frequency (CBF). Application of NH(4)Cl induced profound localized alkalization near cilia, which did not depress ciliary activity, but resulted in strong and prolonged enhancement of CBF. Calmodulin and protein kinase A (PKA) functionality was essential for the alkalization-induced CBF enhancement. We suggest that the ability of airway epithelium to sustain unusually strong but localized cytosolic alkalization near cilia facilitates CBF enhancement through altering the binding constants of Ca2+ to calmodulin and promotion of Ca2+-calmodulin complex formation. The NH4Cl-induced elevations in cytosolic pH and Ca2+ concentration act synergistically to activate calmodulin-dependent processes, cAMP pathway, and, thereby, stimulate CBF.
    Biochimica et Biophysica Acta 07/2008; 1783(6):1102-10. DOI:10.1016/j.bbamcr.2008.02.005 · 4.66 Impact Factor
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