Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle.

Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle. Research Abstract Details 

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Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle. Abstract Text:

Jason R Kovac,Tom Chrones,Stephen M Sims,Jason R Kovac,Tom Chrones,Stephen M Sims,Jason R Kovac,Tom Chrones,Stephen M Sims,

Following smooth muscle excitation and contraction, depletion of intracellular Ca(2+) stores activates capacitative Ca(2+) entry (CCE) to replenish stores and sustain cytoplasmic Ca(2+) (Ca(2+)(i)) elevations. The objectives of the present study were to characterize CCE and the Ca(2+)(i) dynamics underlying human colonic smooth muscle contraction by using tension recordings, fluorescent Ca(2+)-indicator dyes, and patch-clamp electrophysiology. The neurotransmitter acetylcholine (ACh) contracted tissue strips and, in freshly isolated colonic smooth muscle cells (SMCs), caused elevation of Ca(2+)(i) as well as activation of nonselective cation currents. To deplete Ca(2+)(i) stores, the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitors thapsigargin and cyclopiazonic acid were added to a Ca(2+)-free bathing solution. Under these conditions, addition of extracellular Ca(2+) (3 mM) elicited increased tension that was inhibited by the cation channel blockers SKF-96365 (10 muM) and lanthanum (100 muM), suggestive of CCE. In a separate series of experiments on isolated SMCs, SERCA inhibition generated a gradual and sustained inward current. When combined with high-speed Ca(2+)-imaging techniques, the CCE-evoked rise of Ca(2+)(i) was associated with inward currents carrying Ca(2+) that were inhibited by SKF-96365. Regional specializations in Ca(2+) influx and handling during CCE were observed. Distinct "hotspot" regions of Ca(2+) rise and plateau were evident in 70% of cells, a feature not previously recognized in smooth muscle. We propose that store-operated Ca(2+) entry occurs in hotspots contributing to localized Ca(2+) elevations in human colonic smooth muscle.

Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle. Publishing Authors By Initials

JR Kovac,T Chrones,SM Sims,JR Kovac,T Chrones,SM Sims,JR Kovac,T Chrones,SM Sims,

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Temporal and spatial dynamics underlying capacitative calcium entry in human colonic smooth muscle. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Gastrointestinal a

VOLUME: 294

Page Numbers: G88-98

Journal Abbreviation: Am. J. Physiol. Gastrointest.

ISSN: 0193-1857

DAY: 1

MONTH: 11

YEAR: 2007

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LANGUAGE: eng

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AFFILIATION: Schulich School of Medicine and Dentistry, Dept. of Physiology and Pharmacology, Univ. of Western Ontario, London, ON N6A 5C1, Canada. stephen.sims@schulich.uwo.ca).

Country: United States

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MEDLINETA: Am J Physiol Gastrointest Live

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