Molecular basis for pacemaker cells in epithelia

M. Fatima Leite, Keiji Hirata, Thomas Pusl, Angela D. Burgstahler, Keisuke Okazaki, J. Miguel Ortega, Alfredo M. Goes, Marco A M Prado, David C. Spray, Michael H. Nathanson

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Intercellular signaling is highly coordinated in excitable tissues such as heart, but the organization of intercellular signaling in epithelia is less clear. We examined Ca2+ signaling in hepatoma cells expressing the hepatocyte gap junction protein connexin32 (cx32) or the cardiac gap junction protein cx43, plus a fluorescently tagged V1a vasopressin receptor (V1aR). Release of inositol 1,4,5-trisphosphate (InsP3) in wild type cells increased Ca2+ in the injected cell but not in neighboring cells, while the Ca2+ signal spread to neighbors when gap junctions were expressed. Photorelease of caged Ca2+ rather than InsP3 resulted in a small increase in Ca2+ that did not spread to neighbors with or without gap junctions. However, photorelease of Ca2+ in cells stimulated with low concentrations of vasopressin resulted in a much larger increase in Ca2+, which spread to neighbors via gap junctions. Cells expressing tagged V1aR similarly had increased sensitivity to vasopressin, and could signal to neighbors via gap junctions. Higher concentrations of vasopressin elicited Ca2+ signals in all cells. In cx32 or cx43 but not in wild type cells, this signaling was synchronized and began in cells expressing the tagged V1aR Thus, intercellular Ca2+ signals in epithelia are organized by three factors: 1) InsP3 must be generated in each cell to support a Ca2+ signal in that cell; 2) gap junctions are necessary to synchronize Ca2+ signals among cells; and 3) cells with relatively increased expression of hormone receptor will initiate Ca2+ signals and thus serve as pacemakers for their neighbors. Together, these factors may allow epithelia to act in an integrated, organ-level fashion rather than as a collection of isolated cells.

Original languageEnglish (US)
Pages (from-to)16313-16323
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
StatePublished - May 3 2002

Fingerprint

Pacemakers
Vasopressin Receptors
Vasopressins
Connexin 43
Connexins
Epithelium
Cells
Cell signaling
Gap Junctions
Inositol 1,4,5-Trisphosphate
Hormones
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fatima Leite, M., Hirata, K., Pusl, T., Burgstahler, A. D., Okazaki, K., Miguel Ortega, J., ... Nathanson, M. H. (2002). Molecular basis for pacemaker cells in epithelia. Journal of Biological Chemistry, 277(18), 16313-16323. https://doi.org/10.1074/jbc.M109207200

Molecular basis for pacemaker cells in epithelia. / Fatima Leite, M.; Hirata, Keiji; Pusl, Thomas; Burgstahler, Angela D.; Okazaki, Keisuke; Miguel Ortega, J.; Goes, Alfredo M.; Prado, Marco A M; Spray, David C.; Nathanson, Michael H.

In: Journal of Biological Chemistry, Vol. 277, No. 18, 03.05.2002, p. 16313-16323.

Research output: Contribution to journalArticle

Fatima Leite, M, Hirata, K, Pusl, T, Burgstahler, AD, Okazaki, K, Miguel Ortega, J, Goes, AM, Prado, MAM, Spray, DC & Nathanson, MH 2002, 'Molecular basis for pacemaker cells in epithelia', Journal of Biological Chemistry, vol. 277, no. 18, pp. 16313-16323. https://doi.org/10.1074/jbc.M109207200
Fatima Leite M, Hirata K, Pusl T, Burgstahler AD, Okazaki K, Miguel Ortega J et al. Molecular basis for pacemaker cells in epithelia. Journal of Biological Chemistry. 2002 May 3;277(18):16313-16323. https://doi.org/10.1074/jbc.M109207200
Fatima Leite, M. ; Hirata, Keiji ; Pusl, Thomas ; Burgstahler, Angela D. ; Okazaki, Keisuke ; Miguel Ortega, J. ; Goes, Alfredo M. ; Prado, Marco A M ; Spray, David C. ; Nathanson, Michael H. / Molecular basis for pacemaker cells in epithelia. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 18. pp. 16313-16323.
@article{67278e86a8a44202886bd48c0e727c3c,
title = "Molecular basis for pacemaker cells in epithelia",
abstract = "Intercellular signaling is highly coordinated in excitable tissues such as heart, but the organization of intercellular signaling in epithelia is less clear. We examined Ca2+ signaling in hepatoma cells expressing the hepatocyte gap junction protein connexin32 (cx32) or the cardiac gap junction protein cx43, plus a fluorescently tagged V1a vasopressin receptor (V1aR). Release of inositol 1,4,5-trisphosphate (InsP3) in wild type cells increased Ca2+ in the injected cell but not in neighboring cells, while the Ca2+ signal spread to neighbors when gap junctions were expressed. Photorelease of caged Ca2+ rather than InsP3 resulted in a small increase in Ca2+ that did not spread to neighbors with or without gap junctions. However, photorelease of Ca2+ in cells stimulated with low concentrations of vasopressin resulted in a much larger increase in Ca2+, which spread to neighbors via gap junctions. Cells expressing tagged V1aR similarly had increased sensitivity to vasopressin, and could signal to neighbors via gap junctions. Higher concentrations of vasopressin elicited Ca2+ signals in all cells. In cx32 or cx43 but not in wild type cells, this signaling was synchronized and began in cells expressing the tagged V1aR Thus, intercellular Ca2+ signals in epithelia are organized by three factors: 1) InsP3 must be generated in each cell to support a Ca2+ signal in that cell; 2) gap junctions are necessary to synchronize Ca2+ signals among cells; and 3) cells with relatively increased expression of hormone receptor will initiate Ca2+ signals and thus serve as pacemakers for their neighbors. Together, these factors may allow epithelia to act in an integrated, organ-level fashion rather than as a collection of isolated cells.",
author = "{Fatima Leite}, M. and Keiji Hirata and Thomas Pusl and Burgstahler, {Angela D.} and Keisuke Okazaki and {Miguel Ortega}, J. and Goes, {Alfredo M.} and Prado, {Marco A M} and Spray, {David C.} and Nathanson, {Michael H.}",
year = "2002",
month = "5",
day = "3",
doi = "10.1074/jbc.M109207200",
language = "English (US)",
volume = "277",
pages = "16313--16323",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "18",

}

TY - JOUR

T1 - Molecular basis for pacemaker cells in epithelia

AU - Fatima Leite, M.

AU - Hirata, Keiji

AU - Pusl, Thomas

AU - Burgstahler, Angela D.

AU - Okazaki, Keisuke

AU - Miguel Ortega, J.

AU - Goes, Alfredo M.

AU - Prado, Marco A M

AU - Spray, David C.

AU - Nathanson, Michael H.

PY - 2002/5/3

Y1 - 2002/5/3

N2 - Intercellular signaling is highly coordinated in excitable tissues such as heart, but the organization of intercellular signaling in epithelia is less clear. We examined Ca2+ signaling in hepatoma cells expressing the hepatocyte gap junction protein connexin32 (cx32) or the cardiac gap junction protein cx43, plus a fluorescently tagged V1a vasopressin receptor (V1aR). Release of inositol 1,4,5-trisphosphate (InsP3) in wild type cells increased Ca2+ in the injected cell but not in neighboring cells, while the Ca2+ signal spread to neighbors when gap junctions were expressed. Photorelease of caged Ca2+ rather than InsP3 resulted in a small increase in Ca2+ that did not spread to neighbors with or without gap junctions. However, photorelease of Ca2+ in cells stimulated with low concentrations of vasopressin resulted in a much larger increase in Ca2+, which spread to neighbors via gap junctions. Cells expressing tagged V1aR similarly had increased sensitivity to vasopressin, and could signal to neighbors via gap junctions. Higher concentrations of vasopressin elicited Ca2+ signals in all cells. In cx32 or cx43 but not in wild type cells, this signaling was synchronized and began in cells expressing the tagged V1aR Thus, intercellular Ca2+ signals in epithelia are organized by three factors: 1) InsP3 must be generated in each cell to support a Ca2+ signal in that cell; 2) gap junctions are necessary to synchronize Ca2+ signals among cells; and 3) cells with relatively increased expression of hormone receptor will initiate Ca2+ signals and thus serve as pacemakers for their neighbors. Together, these factors may allow epithelia to act in an integrated, organ-level fashion rather than as a collection of isolated cells.

AB - Intercellular signaling is highly coordinated in excitable tissues such as heart, but the organization of intercellular signaling in epithelia is less clear. We examined Ca2+ signaling in hepatoma cells expressing the hepatocyte gap junction protein connexin32 (cx32) or the cardiac gap junction protein cx43, plus a fluorescently tagged V1a vasopressin receptor (V1aR). Release of inositol 1,4,5-trisphosphate (InsP3) in wild type cells increased Ca2+ in the injected cell but not in neighboring cells, while the Ca2+ signal spread to neighbors when gap junctions were expressed. Photorelease of caged Ca2+ rather than InsP3 resulted in a small increase in Ca2+ that did not spread to neighbors with or without gap junctions. However, photorelease of Ca2+ in cells stimulated with low concentrations of vasopressin resulted in a much larger increase in Ca2+, which spread to neighbors via gap junctions. Cells expressing tagged V1aR similarly had increased sensitivity to vasopressin, and could signal to neighbors via gap junctions. Higher concentrations of vasopressin elicited Ca2+ signals in all cells. In cx32 or cx43 but not in wild type cells, this signaling was synchronized and began in cells expressing the tagged V1aR Thus, intercellular Ca2+ signals in epithelia are organized by three factors: 1) InsP3 must be generated in each cell to support a Ca2+ signal in that cell; 2) gap junctions are necessary to synchronize Ca2+ signals among cells; and 3) cells with relatively increased expression of hormone receptor will initiate Ca2+ signals and thus serve as pacemakers for their neighbors. Together, these factors may allow epithelia to act in an integrated, organ-level fashion rather than as a collection of isolated cells.

UR - http://www.scopus.com/inward/record.url?scp=0037013270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037013270&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109207200

DO - 10.1074/jbc.M109207200

M3 - Article

VL - 277

SP - 16313

EP - 16323

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 18

ER -