title: Three-dimensional distribution of cardiac Na+-Ca2+ exchanger and ryanodine receptor during development.
abstract: Mechanisms of cardiac excitation-contraction coupling in neonates are still not clearly defined. Previous work in neonates shows reverse-mode Na(+)-Ca(2+) exchange to be the primary route of Ca(2+) entry during systole and the neonatal sarcoplasmic reticulum to have similar capability as that of adult in storing and releasing Ca(2+). We investigated Na(+)-Ca(2+) exchanger (NCX) and ryanodine receptor (RyR) distribution in developing ventricular myocytes using immunofluorescence, confocal microscopy, and digital image analysis. In neonates, both NCX and RyR clusters on the surface of the cell displayed a short longitudinal periodicity of approximately 0.7 microm. However, by adulthood, both proteins were also found in the interior. In the adult, clusters of NCX on the surface of the cell retained the approximately 0.7-microm periodicity whereas clusters of RyR adopted a longer longitudinal periodicity of approximately 2.0 microm. This suggests that neonatal myocytes also have a peri-M-line RyR distribution that is absent in adult myocytes. NCX and RyR colocalized voxel density was maximal in neonates and declined significantly with ontogeny. We conclude in newborns, Ca(2+) influx via NCX could potentially activate the dense network of peripheral Ca(2+) stores via peripheral couplings, evoking Ca(2+)-induced Ca(2+) release.
authors.affiliation: Cardiac Membrane Research Laboratory, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Pauline
authors.initials: P
authors.lastname: Dan
authors.forename: Eric
authors.initials: E
authors.lastname: Lin
authors.forename: Jingbo
authors.initials: J
authors.lastname: Huang
authors.forename: Perveen
authors.initials: P
authors.lastname: Biln
authors.forename: Glen F
authors.initials: GF
authors.lastname: Tibbits
mesh_terms: D000818:Animals; D001703:Biophysics / Q000379:methods*; D002118:Calcium / Q000378:metabolism; D016000:Cluster Analysis; D018507:Gene Expression Regulation, Developmental; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D015233:Models, Statistical; D032342:Muscle Cells / Q000378:metabolism; D011487:Protein Conformation; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000737:chemistry*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D002118:Calcium