Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles

Masaaki Kurahashi; Violeta Mutafova-Yambolieva; Sang Don Koh; Kenton M Sanders

doi:10.1152/ajpcell.00080.2014

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Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles

Journal article

Open access

Peer reviewed

Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles

Masaaki Kurahashi, Violeta Mutafova-Yambolieva, Sang Don Koh and Kenton M Sanders

American Journal of Physiology: Cell Physiology, Vol.307(6), pp.C561-C570

09/15/2014

DOI: 10.1152/ajpcell.00080.2014

PMCID: PMC4166738

PMID: 25055825

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Abstract

Enteric inhibitory neurotransmission is an important feature of the neural regulation of gastrointestinal motility. Purinergic neurotransmission, via P2Y1 receptors, mediates one phase of inhibitory neural control. For decades, ATP has been assumed to be the purinergic neurotransmitter and smooth muscle cells (SMCs) have been considered the primary targets for inhibitory neurotransmission. Recent experiments have cast doubt on both of these assumptions and suggested that another cell type, platelet-derived growth factor receptor-α-positive (PDGFRα(+)) cells, is the target for purinergic neurotransmission. We compared responses of PDGFRα(+) cells and SMCs to several purine compounds to determine if these cells responded in a manner consistent with enteric inhibitory neurotransmission. ATP hyperpolarized PDGFRα(+) cells but depolarized SMCs. Only part of the ATP response in PDGFRα(+) cells was blocked by MRS 2500, a P2Y1 antagonist. ADP, MRS 2365, β-NAD, and adenosine 5-diphosphate-ribose, P2Y1 agonists, hyperpolarized PDGFRα(+) cells, and these responses were blocked by MRS 2500. Adenosine 5-diphosphate-ribose was more potent in eliciting hyperpolarization responses than β-NAD. P2Y1 agonists failed to elicit responses in SMCs. Small hyperpolarization responses were elicited in SMCs by a small-conductance Ca(2+)-activated K(+) channel agonist, cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, consistent with the low expression and current density of small-conductance Ca(2+)-activated K(+) channels in these cells. Large-amplitude hyperpolarization responses, elicited in PDGFRα(+) cells, but not SMCs, by P2Y1 agonists are consistent with the generation of inhibitory junction potentials in intact muscles in response to purinergic neurotransmission. The responses of PDGFRα(+) cells and SMCs to purines suggest that SMCs are unlikely targets for purinergic neurotransmission in colonic muscles.

Adenosine Diphosphate - metabolism

Adenosine Triphosphate - metabolism

Animals

Colon - cytology

Colon - drug effects

Colon - innervation

Colon - metabolism

Green Fluorescent Proteins - genetics

Green Fluorescent Proteins - metabolism

Membrane Potentials

Mice

Mice, Inbred C57BL

Mice, Transgenic

Muscle, Smooth - cytology

Muscle, Smooth - drug effects

Muscle, Smooth - innervation

Muscle, Smooth - metabolism

Myocytes, Smooth Muscle - drug effects

Myocytes, Smooth Muscle - metabolism

Neural Inhibition

Patch-Clamp Techniques

Purinergic P2Y Receptor Agonists - pharmacology

Receptor, Platelet-Derived Growth Factor alpha - genetics

Receptor, Platelet-Derived Growth Factor alpha - metabolism

Receptors, Purinergic P2Y1 - drug effects

Receptors, Purinergic P2Y1 - metabolism

Recombinant Fusion Proteins - metabolism

Small-Conductance Calcium-Activated Potassium Channels - agonists

Small-Conductance Calcium-Activated Potassium Channels - metabolism

Details

Title: Subtitle: Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles
Creators: Masaaki Kurahashi - University of Nevada Reno
Violeta Mutafova-Yambolieva - University of Nevada Reno
Sang Don Koh - University of Nevada Reno
Kenton M Sanders - University of Nevada Reno
Resource Type: Journal article
Publication Details: American Journal of Physiology: Cell Physiology, Vol.307(6), pp.C561-C570
DOI: 10.1152/ajpcell.00080.2014
PMID: 25055825
PMCID: PMC4166738
ISSN: 0363-6143
eISSN: 1522-1563
Grant note: R01 DK-091336 / NIDDK NIH HHS P01 DK041315 / NIDDK NIH HHS R01 DK091336 / NIDDK NIH HHS
Language: English
Date published: 09/15/2014
Academic Unit: Internal Medicine
Record Identifier: 9984359784402771

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