Propagated endothelial Ca2+ waves and arteriolar dilation in vivo: measurements in Cx40BAC GCaMP2 transgenic mice.
To study endothelial cell (EC)- specific Ca(2+) signaling in vivo we engineered transgenic mice in which the Ca(2+) 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(2+) signals were obtained in Cx40(BAC)-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(2+) fluorescence that propagated along the arteriole with an initial velocity of approximately 116 microm/s (n=28) and decayed over distances up to 974 microm. The local rise in EC Ca(2+) 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 microm), rapidly-conducted vasodilation occurred without changing EC Ca(2+), and additional dilation occurred after arrival of a Ca(2+) wave. In contrast, focal delivery of sodium nitroprusside evoked similar local dilations without Ca(2+) 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(2+) but independent of EC Ca(2+) signaling at remote sites; and (2) a slower complementary dilation associated with a Ca(2+) wave that propagates along the endothelium.
Tallini
Yvonne N
YN
Biomedical Sciences Department, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Brekke
Johan Fredrik
JF
Shui
Bo
B
Doran
Robert
R
Hwang
Seong-min
SM
Nakai
Junichi
J
Salama
Guy
G
Segal
Steven S
SS
Kotlikoff
Michael I
MI
D000818:Animals; D001160:Arterioles / Q000502:physiology*; D020013:Calcium Signaling / Q000235:genetics* / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000502:physiology; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics / Q000502:physiology; D017630:Connexins / Q000235:genetics* / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D052139:Intracellular Calcium-Sensing Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D014664:Vasodilation / Q000235:genetics*; D000097003:Gap Junction alpha-5 Protein
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017630:Connexins; D052139:Intracellular Calcium-Sensing Proteins; D000097003:Gap Junction alpha-5 Protein