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Cellular Biology |
From the Department of Physiology and Danish Biomembrane Research Centre, Aarhus University, Aarhus, Denmark.
Correspondence to Christian Aalkjær, MD, Department of Physiology, Universitetsparken Bldg 160, Aarhus University, 8000 Aarhus C, Denmark. E-mail ca{at}fi.au.dk
AbstractVasomotion is the regular variation in tone of arteries. In our study, we suggest a model for the initiation of vasomotion. We suggest that intermittent release of Ca2+ from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is initially unsynchronized between the vascular smooth muscle cells, becomes synchronized to initiate vasomotion. The synchronization is achieved by an ion current over the cell membrane, which is activated by the oscillating Ca2+ release. This current results in an oscillating membrane potential, which synchronizes the SR in the vessel wall and starts vasomotion. Therefore, the pacemaker of the vascular wall can be envisaged as a diffuse array of individual cytosolic oscillators that become entrained by a reciprocal interaction with the cell membrane. The model is supported by experimental data. Confocal [Ca2+]i imaging and isometric force development in isolated rat resistance arteries showed that low norepinephrine concentrations induced SR-dependent unsynchronized waves of Ca2+ in the vascular smooth muscle. In the presence of the endothelium, the waves converted to global synchronized oscillations of [Ca2+]i after some time, and vasomotion appeared. Synchronization was also seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using the patch-clamp technique and microelectrodes, we showed that Ca2+ release can activate an inward current in isolated smooth muscle cells from the arteries and cause depolarization. These electrophysiological effects of Ca2+ release were cGMP dependent, which is consistent with the possibility that they are important for the cGMP-dependent synchronization. Further support for the model is the observation that a short-lasting current pulse can initiate vasomotion in an unsynchronized artery as expected from the model.
Key Words: calcium imaging calcium waves cGMP synchronization vasomotion
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