Cholinergic regulation of pericyte-containing retinal microvessels.
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 Ca(2+) levels were quantified with the use of 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 Ca(2+)-activated chloride currents and caused pericytes to contract in a Ca(2+)-dependent manner. Most contracting pericytes were near capillary bifurcations. Contraction of a pericyte caused the adjacent capillary lumen to constrict. Thus acetylcholine may serve as a vasoactive signal by regulating pericyte contractility and thereby capillary perfusion in the retina.
Wu
David M
DM
Neuroscience Graduate Program, University of Michigan, Ann Arbor 48105, USA.
Kawamura
Hajime
H
Sakagami
Kenji
K
Kobayashi
Masato
M
Puro
Donald G
DG
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002196:Capillaries / Q000294:innervation / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D016257:Fura-2; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D012171:Retinal Vessels / Q000294:innervation* / Q000502:physiology; D015398:Signal Transduction
D005456:Fluorescent Dyes; D007473:Ion Channels; D018721:Muscarinic Agonists; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D002217:Carbachol; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2