Dynamic modulation of excitation-contraction coupling by protein phosphatases in rat ventricular myocytes
1. The effects of the serine/threonine protein phosphatases (PP) type 1 and 2A on L-type Ca2+ current (ICa) and the intracellular [Ca2+]i transient were examined in rat ventricular myocytes. ICa was measured under voltage clamp using patch-type microelectrodes in the whole-cell mode with the cells i...
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Published in | The Journal of physiology Vol. 493; no. Pt 3; pp. 793 - 800 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
The Physiological Society
15.06.1996
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Subjects | |
Online Access | Get full text |
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Summary: | 1. The effects of the serine/threonine protein phosphatases (PP) type 1 and 2A on L-type Ca2+ current (ICa) and the intracellular
[Ca2+]i transient were examined in rat ventricular myocytes. ICa was measured under voltage clamp using patch-type microelectrodes
in the whole-cell mode with the cells in a steady state of sarcoplasmic reticulum (SR) Ca2+ loading. [Ca2+]i transients were
measured simultaneously using the fluorescent Ca2+ indicator indo-1 (50 microM) which was added to the pipette filling solution
along with PP-1 or PP-2A (4 units ml-1). 2. PP-1 had no effect on the ICa-V relationship but decreased the [Ca2+]i-voltage
relationship (by 43% at 0 mV). PP-2A decreased both ICa-V (by 26% at 0 mV) and the [Ca2+]i transient-voltage (by 65% at 0
mV). Excitation-contraction coupling gain, defined as (delta [Ca2+]i/ICa), was decreased to 43% of control by PP-1 and to
29% of control by PP-2A at-28 mV. 3. Diastolic [Ca2+]i (i.e.[Ca2+]i measured immediately before each voltage clamp pulse)
was not altered by PP-1 or PP-2A and neither phosphatase changed steady-state SR Ca2+ content, as measured with caffeine.
4. We conclude that the reduced [Ca2+]i transient following the application of PP-1 was due to reduced SR Ca2+ release channel
activity. The effects of PP-2A, while more broadly based, were still consistent with a decrease in SR Ca2+ release channel
activity. 5. Our experiments, combined with recent experiments by others, suggest that the basal state of contractility in
heart is dynamically regulated by dephosphorylation and phosphorylation of the SR Ca2+ release channel. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.1996.sp021423 |