Published online before print November 7, 2002, doi: 10.1161/01.RES.0000045940.67060.DD
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© 2002 American Heart Association, Inc.
Cellular Biology |
Spatial and Temporal Inhomogeneities During Ca2+ Release From the Sarcoplasmic Reticulum in Pig Ventricular Myocytes
From the Laboratory of Experimental Cardiology (F.R.H., V.B., P.G.A.V., G.A., K.R.S.) and the Center for Experimental Surgery (K.M.), University of Leuven, Leuven, Belgium; the Institute of Pathophysiology (F.R.H.), University of Essen, Essen, Germany; and the Department of Cardiology (P.G.A.V.), Academic Hospital Maastricht, Maastricht, the Netherlands.
Correspondence to Karin R. Sipido, MD, PhD, Laboratory of Experimental Cardiology, KUL, Campus Gasthuisberg O/N 7th Floor, Herestraat 49, B-3000 Leuven, Belgium. E-mail Karin.Sipido{at}med.kuleuven.ac.be
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 µm 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.
Key Words: ventricular myocytes • calcium • sarcoplasmic reticulum • pigs
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