Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon

Xiaorong Liu, Nancy J. Rusch, Joerg Striessnig, Sushil K. Sarna

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Background & Aims: Circular smooth muscle phasic contractions and tone are suppressed during colonic inflammation, but the contributing factors are poorly understood. This study investigated if the expression level of voltage-gated long-lasting (L-type) Ca2+ channel protein and functional Ca2+ channel current are down-regulated in the circular muscle cells of the inflamed canine colon. Methods: L-type Ca2+ channel expression was compared between normal and inflamed smooth muscle cells by Western immunoblots using an antibody directed against the pore-forming α1C-subunit, and patch-clamp methods were used to evaluate Ca2+ channel current density. Results: The expression of the L-type Ca2+ channel protein was significantly reduced in inflamed compared with normal circular smooth muscle cell membranes, and this finding was associated with suppressed levels of Ca2+ channel current in patch-clamped cells. The L-type Ca2+ channel current in normal and inflamed cells increased proportionately in response to Bay K 8644, but the maximal current density was still lower in the inflamed cells. Acetylcholine increased the L-type Ca2+ channel current in normal but not in inflamed cells. Conclusions: The expression level of L-type Ca2+ channels is down-regulated in the circular smooth muscle cell membranes of the inflamed colon, which may result in reduced Ca2+ influx. The functional and pharmacologic properties of the channels seem normal. Although some Ca2+ channels are still present in the inflamed cells, acetylcholine does not activate these channels, which may be caused by additional upstream defects in the receptor signaling cascade. The down-regulation of L-type Ca2+ channel expression may suppress circular smooth muscle contractions in the inflamed colon and contribute to the abnormalities in motility and digestion observed during inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)480-489
Number of pages10
JournalGastroenterology
Volume120
Issue number2
StatePublished - 2001
Externally publishedYes

Fingerprint

L-Type Calcium Channels
Smooth Muscle Myocytes
Canidae
Colon
Down-Regulation
Muscle Contraction
Acetylcholine
Smooth Muscle
Cell Membrane
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Muscle Cells
Digestion
Proteins
Western Blotting
Inflammation
Antibodies

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Liu, X., Rusch, N. J., Striessnig, J., & Sarna, S. K. (2001). Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon. Gastroenterology, 120(2), 480-489.

Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon. / Liu, Xiaorong; Rusch, Nancy J.; Striessnig, Joerg; Sarna, Sushil K.

In: Gastroenterology, Vol. 120, No. 2, 2001, p. 480-489.

Research output: Contribution to journalArticle

Liu, X, Rusch, NJ, Striessnig, J & Sarna, SK 2001, 'Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon', Gastroenterology, vol. 120, no. 2, pp. 480-489.
Liu, Xiaorong ; Rusch, Nancy J. ; Striessnig, Joerg ; Sarna, Sushil K. / Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon. In: Gastroenterology. 2001 ; Vol. 120, No. 2. pp. 480-489.
@article{db924423c61344b49873b13054e7234b,
title = "Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon",
abstract = "Background & Aims: Circular smooth muscle phasic contractions and tone are suppressed during colonic inflammation, but the contributing factors are poorly understood. This study investigated if the expression level of voltage-gated long-lasting (L-type) Ca2+ channel protein and functional Ca2+ channel current are down-regulated in the circular muscle cells of the inflamed canine colon. Methods: L-type Ca2+ channel expression was compared between normal and inflamed smooth muscle cells by Western immunoblots using an antibody directed against the pore-forming α1C-subunit, and patch-clamp methods were used to evaluate Ca2+ channel current density. Results: The expression of the L-type Ca2+ channel protein was significantly reduced in inflamed compared with normal circular smooth muscle cell membranes, and this finding was associated with suppressed levels of Ca2+ channel current in patch-clamped cells. The L-type Ca2+ channel current in normal and inflamed cells increased proportionately in response to Bay K 8644, but the maximal current density was still lower in the inflamed cells. Acetylcholine increased the L-type Ca2+ channel current in normal but not in inflamed cells. Conclusions: The expression level of L-type Ca2+ channels is down-regulated in the circular smooth muscle cell membranes of the inflamed colon, which may result in reduced Ca2+ influx. The functional and pharmacologic properties of the channels seem normal. Although some Ca2+ channels are still present in the inflamed cells, acetylcholine does not activate these channels, which may be caused by additional upstream defects in the receptor signaling cascade. The down-regulation of L-type Ca2+ channel expression may suppress circular smooth muscle contractions in the inflamed colon and contribute to the abnormalities in motility and digestion observed during inflammatory disorders.",
author = "Xiaorong Liu and Rusch, {Nancy J.} and Joerg Striessnig and Sarna, {Sushil K.}",
year = "2001",
language = "English (US)",
volume = "120",
pages = "480--489",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon

AU - Liu, Xiaorong

AU - Rusch, Nancy J.

AU - Striessnig, Joerg

AU - Sarna, Sushil K.

PY - 2001

Y1 - 2001

N2 - Background & Aims: Circular smooth muscle phasic contractions and tone are suppressed during colonic inflammation, but the contributing factors are poorly understood. This study investigated if the expression level of voltage-gated long-lasting (L-type) Ca2+ channel protein and functional Ca2+ channel current are down-regulated in the circular muscle cells of the inflamed canine colon. Methods: L-type Ca2+ channel expression was compared between normal and inflamed smooth muscle cells by Western immunoblots using an antibody directed against the pore-forming α1C-subunit, and patch-clamp methods were used to evaluate Ca2+ channel current density. Results: The expression of the L-type Ca2+ channel protein was significantly reduced in inflamed compared with normal circular smooth muscle cell membranes, and this finding was associated with suppressed levels of Ca2+ channel current in patch-clamped cells. The L-type Ca2+ channel current in normal and inflamed cells increased proportionately in response to Bay K 8644, but the maximal current density was still lower in the inflamed cells. Acetylcholine increased the L-type Ca2+ channel current in normal but not in inflamed cells. Conclusions: The expression level of L-type Ca2+ channels is down-regulated in the circular smooth muscle cell membranes of the inflamed colon, which may result in reduced Ca2+ influx. The functional and pharmacologic properties of the channels seem normal. Although some Ca2+ channels are still present in the inflamed cells, acetylcholine does not activate these channels, which may be caused by additional upstream defects in the receptor signaling cascade. The down-regulation of L-type Ca2+ channel expression may suppress circular smooth muscle contractions in the inflamed colon and contribute to the abnormalities in motility and digestion observed during inflammatory disorders.

AB - Background & Aims: Circular smooth muscle phasic contractions and tone are suppressed during colonic inflammation, but the contributing factors are poorly understood. This study investigated if the expression level of voltage-gated long-lasting (L-type) Ca2+ channel protein and functional Ca2+ channel current are down-regulated in the circular muscle cells of the inflamed canine colon. Methods: L-type Ca2+ channel expression was compared between normal and inflamed smooth muscle cells by Western immunoblots using an antibody directed against the pore-forming α1C-subunit, and patch-clamp methods were used to evaluate Ca2+ channel current density. Results: The expression of the L-type Ca2+ channel protein was significantly reduced in inflamed compared with normal circular smooth muscle cell membranes, and this finding was associated with suppressed levels of Ca2+ channel current in patch-clamped cells. The L-type Ca2+ channel current in normal and inflamed cells increased proportionately in response to Bay K 8644, but the maximal current density was still lower in the inflamed cells. Acetylcholine increased the L-type Ca2+ channel current in normal but not in inflamed cells. Conclusions: The expression level of L-type Ca2+ channels is down-regulated in the circular smooth muscle cell membranes of the inflamed colon, which may result in reduced Ca2+ influx. The functional and pharmacologic properties of the channels seem normal. Although some Ca2+ channels are still present in the inflamed cells, acetylcholine does not activate these channels, which may be caused by additional upstream defects in the receptor signaling cascade. The down-regulation of L-type Ca2+ channel expression may suppress circular smooth muscle contractions in the inflamed colon and contribute to the abnormalities in motility and digestion observed during inflammatory disorders.

UR - http://www.scopus.com/inward/record.url?scp=0035124729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035124729&partnerID=8YFLogxK

M3 - Article

C2 - 11159888

AN - SCOPUS:0035124729

VL - 120

SP - 480

EP - 489

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 2

ER -