title: Diabetes-induced inhibition of voltage-dependent calcium channels in the retinal microvasculature: role of spermine.
abstract: OBJECTIVE
  Although decentralized control of blood flow is particularly important in the retina, knowledge of the functional organization of the retinal microvasculature is limited. Here, the authors characterized the distribution and regulation of L-type voltage-dependent calcium channels (VDCCs) within the most decentralized operational complex of the retinal vasculature--the feeder vessel/capillary unit--which consists of a capillary network plus the vessel linking it with a myocyte-encircled arteriole.
  
  
  METHODS
  Perforated-patch recordings, calcium-imaging, and time-lapse photography were used to assess VDCC-dependent changes in ionic currents, intracellular calcium, abluminal cell contractility, and lumen diameter, in microvascular complexes freshly isolated from the rat retina.
  
  
  RESULTS
  Topographical heterogeneity was found in the distribution of functional VDCCs; VDCC activity was markedly greater in feeder vessels than in capillaries. Experiments showed that this topographical distribution occurs, in large part, because of the inhibition of capillary VDCCs by a mechanism dependent on the endogenous polyamine spermine. An operational consequence of functional VDCCs predominantly located in the feeder vessels is that voltage-driven vasomotor responses are generated chiefly in this portion of the feeder vessel/capillary unit. However, early in the course of diabetes, this ability to generate voltage-driven vasomotor responses becomes profoundly impaired because of the inhibition of feeder vessel VDCCs by a spermine-dependent mechanism.
  
  
  CONCLUSIONS
  The regulation of VDCCs by endogenous spermine not only plays a critical role in establishing the physiological organization of the feeder vessel/capillary unit, but also may contribute to dysfunction of this decentralized operational unit in the diabetic retina.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Fudan University, Shanghai, China.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Masato
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Eisuke
authors.initials: E
authors.lastname: Ishizaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Minami
authors.forename: Kozo
authors.initials: K
authors.lastname: Katsumura
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Liao
authors.forename: David M
authors.initials: DM
authors.lastname: Wu
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Donald G
authors.initials: DG
authors.lastname: Puro
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000503:physiopathology; D016257:Fura-2 / Q000031:analogs & derivatives; D007124:Immunoenzyme Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D012171:Retinal Vessels / Q000378:metabolism*; D013096:Spermine / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D020746:Calcium Channels, L-Type; C049925:fura-2-am; D013096:Spermine; D002118:Calcium; D016257:Fura-2