UMMS Affiliation

Department of Physiology

Date

6-2-2005

Document Type

Article

Subjects

Acetylcholine; Animals; Arterioles; Bronchi; Caffeine; Calcium Channel Blockers; Calcium Signaling; Cells, Cultured; Central Nervous System Stimulants; Extracellular Space; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Muscle Contraction; Muscle, Smooth, Vascular; Nifedipine; Potassium Chloride; Serotonin; Spectrometry, Fluorescence; Stimulation, Chemical

Disciplines

Cellular and Molecular Physiology | Physiology

Abstract

Increased resistance of airways or blood vessels within the lung is associated with asthma or pulmonary hypertension and results from contraction of smooth muscle cells (SMCs). To study the mechanisms regulating these contractions, we developed a mouse lung slice preparation containing bronchioles and arterioles and used phase-contrast and confocal microscopy to correlate the contractile responses with changes in [Ca(2+)](i) of the SMCs. The airways are the focus of this study. The agonists, 5-hydroxytrypamine (5-HT) and acetylcholine (ACH) induced a concentration-dependent contraction of the airways. High concentrations of KCl induced twitching of the airway SMCs but had little effect on airway size. 5-HT and ACH induced asynchronous oscillations in [Ca(2+)](i) that propagated as Ca(2+) waves within the airway SMCs. The frequency of the Ca(2+) oscillations was dependent on the agonist concentration and correlated with the extent of sustained airway contraction. In the absence of extracellular Ca(2+) or in the presence of Ni(2+), the frequency of the Ca(2+) oscillations declined and the airway relaxed. By contrast, KCl induced low frequency Ca(2+) oscillations that were associated with SMC twitching. Each KCl-induced Ca(2+) oscillation consisted of a large Ca(2+) wave that was preceded by multiple localized Ca(2+) transients. KCl-induced responses were resistant to neurotransmitter blockers but were abolished by Ni(2+) or nifedipine and the absence of extracellular Ca(2+). Caffeine abolished the contractile effects of 5-HT, ACH, and KCl. These results indicate that (a) 5-HT and ACH induce airway SMC contraction by initiating Ca(2+) oscillations, (b) KCl induces Ca(2+) transients and twitching by overloading and releasing Ca(2+) from intracellular stores, (c) a sustained, Ni(2+)-sensitive, influx of Ca(2+) mediates the refilling of stores to maintain Ca(2+) oscillations and, in turn, SMC contraction, and (d) the magnitude of sustained airway SMC contraction is regulated by the frequency of Ca(2+) oscillations.

Rights and Permissions

Citation: J Gen Physiol. 2005 Jun;125(6):535-53. Link to article on publisher's site

DOI of Published Version

10.1085/jgp.200409216

Related Resources

Link to Article in PubMed

Journal Title

The Journal of general physiology

PubMed ID

15928401

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