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1 Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA
2 Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA
3 Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: dgpuro{at}umich.edu.
The aim of this study was to test the hypothesis that the neurotransmitter acetylcholine regulates the function of pericyte-containing retinal microvessels. A vasoactive role for acetylcholine is suggested by the presence of muscarinic receptors on pericytes, which are abluminally positioned contractile cells that may regulate capillary perfusion. However, little is known about the response of retinal microvessels to this neurotransmitter. Here, we assessed the effects of cholinergic agonists on microvessels freshly isolated from the adult rat retina. Ionic currents were monitored via perforated-patch pipettes; intracellular calcium levels were quantified using fura-2, and microvascular contractions were visualized with the aid of time-lapse photography. We found that activation of muscarinic receptors elevated pericyte calcium levels, increased depolarizing calcium-activated chloride currents and caused pericytes to contract in a calcium-dependent manner. Most contracting pericytes were near capillary bifurcations. Associated with pericyte contractions, capillary lumens constricted. Thus, acetylcholine may serve as a vasoactive signal by regulating pericyte contractility and thereby, capillary perfusion in the retina.
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