Propagated endothelial Ca2+ waves and arteriolar dilation in vivo: Measurements in Cx40BAC-GCaMP2 transgenic mice

Yvonne N. Tallini, Johan Fredrik Brekke, Bo Shui, Robert Doran, Seong Min Hwang, Junichi Nakai, Guy Salama, Steven S. Segal, Michael I. Kotlikoff

Research output: Contribution to journalArticlepeer-review

151 Citations (Scopus)

Abstract

To study endothelial cell (EC)- specific Ca signaling in vivo we engineered transgenic mice in which the Ca sensor GCaMP2 is placed under control of endogenous connexin40 (Cx40) transcription regulatory elements within a bacterial artificial chromosome (BAC), resulting in high sensor expression in arterial ECs, atrial myocytes, and cardiac Purkinje fibers. High signal/noise Ca signals were obtained in Cx40-GCaMP2 mice within the ventricular Purkinje cell network in vitro and in ECs of cremaster muscle arterioles in vivo. Microiontophoresis of acetylcholine (ACh) onto arterioles triggered a transient increase in EC Ca fluorescence that propagated along the arteriole with an initial velocity of ≈116 μm/s (n=28) and decayed over distances up to 974 μm. The local rise in EC Ca was followed (delay, 830±60 ms; n=8) by vasodilation that conducted rapidly (mm/s), bidirectionally, and into branches for distances exceeding 1 mm. At intermediate distances (300 to 600 μm), rapidly-conducted vasodilation occurred without changing EC Ca, and additional dilation occurred after arrival of a Ca wave. In contrast, focal delivery of sodium nitroprusside evoked similar local dilations without Ca signaling or conduction. We conclude that in vivo responses to ACh in arterioles consists of 2 phases: (1) a rapidly-conducted vasodilation initiated by a local rise in EC Ca but independent of EC Ca signaling at remote sites; and (2) a slower complementary dilation associated with a Ca wave that propagates along the endothelium.

Original languageEnglish
Pages (from-to)1300-1309
Number of pages10
JournalCirculation research
Volume101
Issue number12
DOIs
Publication statusPublished - 2007 Dec
Externally publishedYes

Keywords

  • Bacterial artificial chromosome
  • Calcium imaging
  • Microcirculation
  • Purkinje cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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