Title of article :
Sphingosine Effects on the Contractile Behavior of Skinned Cardiac Myocytes
Author/Authors :
Robert J. Webster، نويسنده , , Roger A. Sabbadini، نويسنده , , Christine A. Dettbarn، نويسنده , , Paul J. Paolini، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 1994
Pages :
18
From page :
1273
To page :
1290
Abstract :
Sphingosine modulates myocytes beating behavior by acting on the sarcoplasmic reticulum calcium release channel, the ryanodine receptor. Chemically skinned myocytes isolated from adult rabbit ventricles exhibited spontaneous asynchonous contractions in response to micromolar levels of calcium. These cells do not have a functional sarcolemma but exhibit spontaneous contraction-relaxation cycles which are controlled by the sarcoplasmic reticulum. The intracellular second messenger, sphingosine, significantly reduced myocytes beat frequency in a biphasic manner with an IC50 of c. 0.5 μM. A computerized video-enhancement micrography system was used to determine the effect of sphingosine on sarcomere contractile parameters and to determine the potential source of the altered beating behavior produced by sphingosine. Contraction parameters related to sarcomere shortening were unaffected by sphingosine in the submicromolar range, suggesting that sphingosine had no effect on the contractile machinery itself. However submicromolar sphingosine had a significant inhibitory effect on the spread of activation from sarcomere to sarcomere in these cells. Activation waves were propagated with an average velocity of 331 and 199 μ/s in control and sphingosine (0.58 μM) treated cells, respectively. Permeabilized myocyte calcium uptake was markedly increased by treatment with sphingosine, consistent with an inhibitory effect of sphingosine on sarcoplasmic calcium release. Sphingosine blocked calcium-induced calcium release from isolated cardiac sarcoplasmic reticulum membranes containing the ryanodine receptor. The results suggest that the site of sphingosine action on calcium signaling and beating behavior in the cardiac cell is the sarcoplasmic reticulum ryanodine receptor. By inhibiting channel opening sphingosine may increase the calcium threshold necessary to trigger calcium-induced calcium release, thus modulating cardiac excitation-contraction coupling.
Keywords :
Sphingosine , Calcium-induced calcium release , Sarcomere activation waves , ryanodine receptor , Sarcomere contractility , Skinned cardiac myocytes
Journal title :
Journal of Molecular and Cellular Cardiology
Serial Year :
1994
Journal title :
Journal of Molecular and Cellular Cardiology
Record number :
525190
Link To Document :
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