title: Spatial and temporal inhomogeneities during Ca2+ release from the sarcoplasmic reticulum in pig ventricular myocytes.
abstract: The [Ca2+]i transient of ventricular myocytes during normal excitation-contraction coupling is the summation of primary Ca2+ release events, which originate at the junction of the sarcoplasmic reticulum (SR) and the T-tubular system. Studies in small mammals have shown a high density of release sites, but little is known of larger mammals. We have studied the spatial distribution of SR Ca2+ release in pig ventricular myocytes using a confocal microscopy. In 69 of 107 cells, large inhomogeneities of Ca2+ release were observed along the longitudinal scan line. Areas where the increase of [Ca2+]i was delayed (time to 50% of peak F/F0 [where F indicates fluorescence intensity, and F0 indicates F at rest] was 26+/-1 ms in delayed areas versus 11+/-2 ms in early areas) and smaller (peak F/F0 was 2.27+/-0.10 for delayed areas versus 2.69+/-0.13 for early areas; n=13 cells, P<0.05) could be up to 26 microm wide. The sum of all delayed areas could make up to 55% of the line scan. The spatial pattern was constant during steady-state stimulation and was not altered by enhancing Ca2+ channel opening or SR Ca2+ content (Bay K8644, isoproterenol). Imaging of sarcolemmal membranes revealed several areas devoid of T tubules, but SR Ca2+ release channels were homogeneously distributed. In contrast, compared with pig myocytes, mouse myocytes had a very dense T-tubular network, no large inhomogeneities of release, and a faster rate of rise of [Ca2+]i. In conclusion, in pig ventricular myocytes, areas of delayed release are related to regional absence of T tubules but not ryanodine receptors. This lower number of functional couplons contributes to a slower overall rate of rise of [Ca2+]i.
authors.affiliation: Laboratory of Experimental Cardiology, University of Leuven, Leuven, Belgium.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Heinzel
authors.forename: Virginie
authors.initials: V
authors.lastname: Bito
authors.forename: Paul G A
authors.initials: PG
authors.lastname: Volders
authors.forename: Gudrun
authors.initials: G
authors.lastname: Antoons
authors.forename: Kanigula
authors.initials: K
authors.lastname: Mubagwa
authors.forename: Karin R
authors.initials: KR
authors.lastname: Sipido
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology; D002469:Cell Separation; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013552:Swine
chemical_list: D000318:Adrenergic beta-Agonists; D002120:Calcium Channel Agonists; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D007545:Isoproterenol; D002118:Calcium