Imaging cellular signals in the heart in vivo: Cardiac expression of the high-signal Ca2+ indicator GCaMP2

Yvonne M. Tallini, Masamichi Ohkura, Bum Rak Choi, Guangju Ji, Keiji Imoto, Robert Doran, Jane Lee, Patricia Plan, Jason Wilson, Hong Bo Xin, Atsushi Sanbe, James Gulick, John Mathai, Jeffrey Robbins, Guy Salama, Junichi Nakai, Michael I. Kotlikoff

Research output: Contribution to journalArticlepeer-review

340 Citations (Scopus)

Abstract

Genetically encoded sensor proteins provide unique opportunities to advance the understanding of complex cellular interactions in physiologically relevant contexts; however, previously described sensors have proved to be of limited use to report cell signaling in vivo in mammals. Here, we describe an improved Ca2+ sensor, GCaMP2, its inducible expression in the mouse heart, and its use to examine signaling in heart cells in vivo. The high brightness and stability of GCaMP2 enable the measurement of myocyte Ca2+ transients in all regions of the beating mouse heart and prolonged pacing and mapping studies in isolated, perfused hearts. Transgene expression is efficiently temporally regulated in cardiomyocyte GCaMP2 mice, allowing recording of in vivo signals 4 weeks after transgene induction. High-resolution imaging of Ca 2+ waves in GCaMP2-expressing embryos revealed key aspects of electrical conduction in the preseptated heart. At embryonic day (e.d.) 10.5, atrial and ventricular conduction occur rapidly, consistent with the early formation of specialized conduction pathways. However, conduction is markedly slowed through the atrioventricular canal in the e.d. 10.5 heart, forming the basis for an effective atrioventricular delay before development of the AV node, as rapid ventricular activation occurs after activation of the distal AV canal tissue. Consistent with the elimination of the inner AV canal muscle layer at e.d. 13.5, atrioventricular conduction through the canal was abolished at this stage. These studies demonstrate that GCaMP2 will have broad utility in the dissection of numerous complex cellular interactions in mammals, in vivo.

Original languageEnglish
Pages (from-to)4753-4758
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number12
DOIs
Publication statusPublished - 2006 Mar 21
Externally publishedYes

Keywords

  • Atrioventricular node
  • Ca imaging
  • Fluorescent Ca sensor
  • Genetic sensor
  • Heart development

ASJC Scopus subject areas

  • General

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