|
Originally published In Press as doi:10.1074/jbc.M200829200 on March 14, 2002
J. Biol. Chem., Vol. 277, Issue 21, 18586-18591, May 24, 2002
Molecular and Functional Characterization of a Murine
Calcium-activated Chloride Channel Expressed in Smooth Muscle*
Randolph C.
Elble §,
Guangju
Ji¶,
Keith
Nehrke ,
John
DeBiasio ,
Paul D.
Kingsley**,
Michael I.
Kotlikoff§¶, and
Bendicht U.
Pauli
From the Cancer Biology Laboratories and Departments
of Molecular Medicine and ¶ Biomedical Sciences, Cornell
University College of Veterinary Medicine, Ithaca, New York 14853 and
Center for Oral Biology and ** Center for Human
Genetics and Molecular Pediatric Disease, Aab Institute for Biomedical
Research, University of Rochester,
Rochester, New York 14642
To identify the gene products responsible for the
calcium-activated chloride current in smooth muscle, reverse
transcription-PCR with degenerate primers was performed on mouse
intestine and other organs. A new member of the CLCA gene family was
identified, mCLCA4, that is expressed preferentially in organs
containing a high percentage of smooth muscle cells, including
intestine, stomach, uterus, bladder, and aorta. Reverse
transcription-PCR using template RNA prepared from mouse bladder and
stomach smooth muscle layers dissected free of mucosa yielded
mCLCA4-specific bands. In situ hybridization with an
mCLCA4-specific probe confirmed prominent expression in smooth muscle
of major vessels of the heart but not cardiac muscle. High expression
was also detected in the gastrointestinal tract, in bronchioles, and in
aortic and lung endothelial cells. Transient expression of mCLCA4 in
293T cells resulted in the appearance of a prominent calcium-activated
chloride current. Whole-cell currents activated by ionomycin or
methacholine were anion-selective and showed minimal rectification or
voltage-dependent gating. Similar to endogenous currents in
smooth muscle cells, methacholine-induced currents were transient, and
spontaneous transient inward currents were occasionally observed at
resting membrane potentials. These results link calcium-activated
chloride channels in smooth muscle with a gene family whose members
have been implicated in cystic fibrosis, cancer, and asthma.
*
This work was supported by United States Army Breast Cancer
Research Fund Grant DAMD17-00-1-0219 (to R. C. E.), NCI, National Institutes of Health (NIH) Public Health Service (PBS) Grant CA47668 (to B. U. P.), PHS Grant DE09692 (to K. N.), and NIH PHS Grants HL45239, HL41084, and DK58795 (to M. I. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY00827.
§
To whom correspondence should be addressed. To R. C. E.: Tel.:
607-253-3324; Fax: 607-253-3708; E-mail: rce3@cornell.edu. To
M. I. K.: Tel.: 607-253-3336; Fax: 607-253-3317; E-mail:
mik7@cornell.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
J. Song, X. Zhang, Z. Qi, G. Sun, S. Chi, Z. Zhu, J. Ren, Z. Qiu, K. Liu, L. Myatt, et al.
Cloning and Characterization of a Calcium-Activated Chloride Channel in Rat Uterus
Biol Reprod,
April 1, 2009;
80(4):
788 - 794.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Huan, K. S. Greene, B. Shui, G. Spizz, H. Sun, R. M. Doran, P. J. Fisher, M. S. Roberson, R. C. Elble, and M. I. Kotlikoff
mCLCA4 ER processing and secretion requires luminal sorting motifs
Am J Physiol Cell Physiol,
July 1, 2008;
295(1):
C279 - C287.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. K. Bothe, J. Braun, L. Mundhenk, and A. D. Gruber
Murine mCLCA6 Is an Integral Apical Membrane Protein of Non-goblet Cell Enterocytes and Co-localizes With the Cystic Fibrosis Transmembrane Conductance Regulator
J. Histochem. Cytochem.,
May 1, 2008;
56(5):
495 - 509.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. C. Elble, V. Walia, H.-c. Cheng, C. J. Connon, L. Mundhenk, A. D. Gruber, and B. U. Pauli
The Putative Chloride Channel hCLCA2 Has a Single C-terminal Transmembrane Segment
J. Biol. Chem.,
October 6, 2006;
281(40):
29448 - 29454.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Mundhenk, M. Alfalah, R. C. Elble, B. U. Pauli, H. Y. Naim, and A. D. Gruber
Both Cleavage Products of the mCLCA3 Protein Are Secreted Soluble Proteins
J. Biol. Chem.,
October 6, 2006;
281(40):
30072 - 30080.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J-W Jeong, K Y Lee, J P Lydon, and F J DeMayo
Steroid hormone regulation of Clca3 expression in the murine uterus.
J. Endocrinol.,
June 1, 2006;
189(3):
473 - 484.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Nakano, H. Inoue, S. Fukuyama, K. Matsumoto, M. Matsumura, M. Tsuda, T. Matsumoto, H. Aizawa, and Y. Nakanishi
Niflumic Acid Suppresses Interleukin-13-induced Asthma Phenotypes
Am. J. Respir. Crit. Care Med.,
June 1, 2006;
173(11):
1216 - 1221.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Robert, C. Norez, and F. Becq
Disruption of CFTR chloride channel alters mechanical properties and cAMP-dependent Cl- transport of mouse aortic smooth muscle cells
J. Physiol.,
October 15, 2005;
568(2):
483 - 495.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. E. Loewen and G. W. Forsyth
Structure and Function of CLCA Proteins
Physiol Rev,
July 1, 2005;
85(3):
1061 - 1092.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. R. Beckley, B. U. Pauli, and R. C. Elble
Re-expression of Detachment-inducible Chloride Channel mCLCA5 Suppresses Growth of Metastatic Breast Cancer Cells
J. Biol. Chem.,
October 1, 2004;
279(40):
41634 - 41641.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. R. Evans, W. B. Thoreson, and C. L. Beck
Molecular and Functional Analyses of Two New Calcium-activated Chloride Channel Family Members from Mouse Eye and Intestine
J. Biol. Chem.,
October 1, 2004;
279(40):
41792 - 41800.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. H. Boese, O. Aziz, N. L. Simmons, and M. A. Gray
Kinetics and regulation of a Ca2+-activated Cl- conductance in mouse renal inner medullary collecting duct cells
Am J Physiol Renal Physiol,
April 1, 2004;
286(4):
F682 - F692.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Qu, R. Fischmeister, and C. Hartzell
Mouse Bestrophin-2 Is a Bona fide Cl- Channel: Identification of a Residue Important in Anion Binding and Conduction
J. Gen. Physiol.,
March 29, 2004;
123(4):
327 - 340.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Wrayzx, K. Jones, S. Kupittayanant, Y. Li, A. Matthew, E. Monir-Bishty, K. Noble, S. J. Pierce, S. Quenby, and A. V. Shmygol
Calcium Signaling and Uterine Contractility
Reproductive Sciences,
July 1, 2003;
10(5):
252 - 264.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Gustincich, S. Batalov, K. W. Beisel, H. Bono, P. Carninci, C. F. Fletcher, S. Grimmond, N. Hirokawa, E. D. Jarvis, T. Jegla, et al.
Analysis of the Mouse Transcriptome for Genes Involved in the Function of the Nervous System
Genome Res.,
June 1, 2003;
13(6):
1395 - 1401.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|