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Resolution of Ca 2+ dynamics underlying conducted vasodilation: The Ca 2+ wave.
Author(s) -
Uhrenholt Torben R.,
Domeier Timothy L.,
Segal Steven S.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a277
Subject(s) - hyperpolarization (physics) , vasodilation , chemistry , biophysics , anatomy , cremaster muscle , medicine , microcirculation , biology , stereochemistry , nuclear magnetic resonance spectroscopy
Conducted vasodilation coordinates blood flow control in microvascular resistance networks. In isolated pressurized (75 mmHg) feed arteries (~70 μm diameter) of the hamster retractor muscle, focal delivery of ACh initiates hyperpolarization that conducts rapidly along the endothelium and into smooth muscle through gap junction channels. In endothelial cells (EC), ACh increases [Ca 2+ ] i and initiates hyperpolarization. However, [Ca 2+ ] i dynamics along the vessel during conduction have not been established. We tested the hypothesis that the conduction of vasodilation is associated with an increase in EC [Ca 2+ ] i along the vessel wall. Feed arteries were loaded with Fluo‐4 and observed up to 700 μm from the stimulus site using LSC microscopy. At the site of ACh delivery (1 μm pipette, 500 ms), EC [Ca 2+ ] i increased within 2 s and was accompanied by an immediate fall in [Ca 2+ ] i along the entire vessel; nearly 2 s elapsed before dilation of the entire segment ensued. A secondary ‘wave’ of [Ca 2+ ] i originating from the stimulus site traveled along the endothelium for > 200 μm (115 ± 14 μm/s; n=6) during this 2 s period. Remarkably, the onset of vasodilation beyond 400 μm upstream progressively preceded arrival of the Ca 2+ wave. These findings reveal that conduction of the initial Ca 2+ ‐induced hyperpolarization mediates the rapid fall in [Ca 2+ ] i with a latency of ~ 2 s before smooth muscle relaxation. Instead of driving conducted vasodilation, the ensuing Ca 2+ wave may sustain smooth muscle relaxation through promoting release of EC‐derived autacoids. (Support: NIH RO1 HL56786 & Danish MRC).