title: Ca(2+) sparks promote myogenic tone in retinal arterioles.
abstract: OBJECTIVE
  Ca(2+) imaging reveals subcellular Ca(2+) sparks and global Ca(2+) waves/oscillations in vascular smooth muscle. It is well established that Ca(2+) sparks can relax arteries, but we have previously reported that sparks can summate to generate Ca(2+) waves/oscillations in unpressurized retinal arterioles, leading to constriction. We have extended these studies to test the functional significance of Ca(2+) sparks in the generation of myogenic tone in pressurized arterioles.
  
  
  METHODS
  Isolated retinal arterioles (25-40 μm external diameter) were pressurized to 70 mmHg, leading to active constriction. Ca(2+) signals were imaged from arteriolar smooth muscle in the same vessels using Fluo4 and confocal laser microscopy.
  
  
  RESULTS
  Tone development was associated with an increased frequency of Ca(2+) sparks and oscillations. Vasomotion was observed in 40% of arterioles and was associated with synchronization of Ca(2+) oscillations, quantifiable as an increased cross-correlation coefficient. Inhibition of Ca(2+) sparks with ryanodine, tetracaine, cyclopiazonic acid or nimodipine, or following removal of extracellular Ca(2+) , resulted in arteriolar relaxation. Cyclopiazonic acid-induced dilatation was associated with decreased Ca(2+) sparks and oscillations but with a sustained rise in the mean global cytoplasmic [Ca(2+) ] ([Ca(2+) ]c ), as measured using Fura2 and microfluorimetry.
  
  
  CONCLUSIONS
  This study provides direct evidence that Ca(2+) sparks can play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of vascular smooth muscle. Changes in vessel tone in the presence of cyclopiazonic acid correlated more closely with changes in spark and oscillation frequency than global [Ca(2+) ]c , underlining the importance of frequency-modulated signalling in vascular smooth muscle.
authors.affiliation: Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: J
authors.initials: J
authors.lastname: Kur
authors.forename: P
authors.initials: P
authors.lastname: Bankhead
authors.forename: C N
authors.initials: CN
authors.lastname: Scholfield
authors.forename: T M
authors.initials: TM
authors.lastname: Curtis
authors.forename: J G
authors.initials: JG
authors.lastname: McGeown
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013748:Tetracaine / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D007211:Indoles; D019837:Ryanodine Receptor Calcium Release Channel; D013748:Tetracaine; D012433:Ryanodine; D009553:Nimodipine; D002118:Calcium; C000543:cyclopiazonic acid