Journal article
A functional role for the 'fibroblast-like cells' in gastrointestinal smooth muscles
The Journal of physiology, Vol.589(3), pp.697-710
02/01/2011
DOI: 10.1113/jphysiol.2010.201129
PMCID: PMC3055552
PMID: 21173079
Abstract
Non-technical summary
Smooth muscles, as in the gastrointestinal tract, are composed of several types of cells. Gastrointestinal muscles contain smooth muscle cells, enteric neurons, glial cells, immune cells, and various classes of interstitial cells. One type of interstitial cell, referred to as 'fibroblast-like cells' by morphologists, are common, but their function is unknown. These cells are found near the terminals of enteric motor neurons, suggesting they could have a role in generating neural responses that help control gastrointestinal movements. We used a novel mouse with bright green fluorescent protein expressed specifically in the fibroblast-like cells to help us identify these cells in the mixture of cells obtained when whole muscles are dispersed with enzymes. We isolated these cells and found they respond to a major class of inhibitory neurotransmitters - purines. We characterized these responses, and our results provide a new hypothesis about the role of fibroblast-like cells in smooth muscle tissues.Morphologists have described 'fibroblast-like cells' (FLCs) in smooth muscles. In the gastrointestinal tract, FLCs are distributed along processes of enteric motor neurons and between the circular and longitudinal muscle layers. They are close to nerve varicosities and make gap junctions with smooth muscle cells. They are labelled with antibodies for platelet derived growth factor receptor alpha (PDGFR alpha) and small conductance Ca2+-activated K+ (SK3) channels. We used transgenic mice with constitutive expression of enhanced green fluorescent protein (eGFP) in PDGFR alpha+ cells to isolate and study the function of PDGFR alpha+ cells as possible mediators of purinergic neurotransmission. PDGFR alpha+ cells expressed purine receptors (P2Y1) and SK3 channels abundantly. Under whole cell voltage clamp some PDGFR alpha+ cells generated large amplitude spontaneous transient outward currents that were blocked by apamin (300 nm). Dialysis of cells with Ca2+ (500 nm) activated large amplitude K+ currents that were also blocked by apamin. Application of adenosine triphosphate (ATP), adenine diphosphate (ADP) or beta-nicotinamide adenine dinucleotide (beta-NAD) (1-1000 mu m) activated large amplitude, apamin-sensitive K+ currents in PDGFR alpha+ cells that were blocked by the P2Y1 antagonist MRS2500 (1 mu m). Responses to purines were not elicited in smooth muscle cells under equivalent conditions, and only very small outward currents were elicited under optimized conditions (e.g. permeabilized patches and high concentrations of ATP; 1 mm). These data show that PDGFR alpha+ cells are a novel class of excitable cells with large current densities attributable to SK channels and the molecular and ionic apparatus to mediate enteric inhibitory responses to purines in GI muscles.
Details
- Title: Subtitle
- A functional role for the 'fibroblast-like cells' in gastrointestinal smooth muscles
- Creators
- Masaaki Kurahashi - University of Nevada RenoHaifeng Zheng - University of Nevada RenoLaura Dwyer - University of Nevada RenoSean M. Ward - University of Nevada RenoSang Don Koh - University of Nevada RenoKenton M. Sanders - University of Nevada Reno
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.589(3), pp.697-710
- Publisher
- Wiley
- DOI
- 10.1113/jphysiol.2010.201129
- PMID
- 21173079
- PMCID
- PMC3055552
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Number of pages
- 14
- Grant note
- DK41315; S10 RR16871 / NIH1 S10RR016871 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) P01DK041315 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) DK41315 / University of Nevada, Reno
- Language
- English
- Date published
- 02/01/2011
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984359580602771
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