Abstract
We investigated the role of Ca/calmodulin-dependent protein kinase (CaMKII) in relaxation and cytosolic free [Ca] ([Ca](i)) decline during steady-state (SS) and postrest (PR) twitches in intact rat ventricular myocytes. Half-time of mechanical relaxation and time constant of [Ca](i) decline (τ) were twofold greater during PR than with SS at 1 Hz. This difference was 1) abolished by inhibition of sarcoplasmic reticulum (SR) Ca accumulation by thapsigargin or caffeine; 2) greater at higher stimulation frequency and extracellular [Ca], which affected only SS τ; 3) abolished by the protein phosphatase inhibitor okadaic acid (10 μM, which selectively accelerated [Ca](i) decline during PR); 4) still present during stimulation or inhibition of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) by 10 μM forskolin or 1 μM H-89, respectively (SS and PR T values were abbreviated and prolonged, respectively); and 5) suppressed by 10 μM KN-62, a selective inhibitor of CaMKII, which selectively prolonged [Ca](i) decline during SS twitches. Both protein kinase inhibitors were also shown to decrease the SR Ca-uptake rate in digitonin-permeabilized rat myocytes. We conclude that CaMKII plays a major role in modulation of relaxation in rat ventricular myocytes, enhancing SR Ca uptake in a activity- dependent fashion. Our results are also compatible with a background, activity-independent stimulation of SR Ca uptake by PKA in intact rat myocytes.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 268 |
| Issue number | 2 37-2 |
| State | Published - 1995 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Physiology
- Agricultural and Biological Sciences(all)
Cite this
CaMKII is responsible for activity-dependent acceleration of relaxation in rat ventricular myocytes. / Bassani, R. A.; Mattiazzi, A.; Bers, Donald M.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 268, No. 2 37-2, 1995.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CaMKII is responsible for activity-dependent acceleration of relaxation in rat ventricular myocytes
AU - Bassani, R. A.
AU - Mattiazzi, A.
AU - Bers, Donald M
PY - 1995
Y1 - 1995
N2 - We investigated the role of Ca/calmodulin-dependent protein kinase (CaMKII) in relaxation and cytosolic free [Ca] ([Ca](i)) decline during steady-state (SS) and postrest (PR) twitches in intact rat ventricular myocytes. Half-time of mechanical relaxation and time constant of [Ca](i) decline (τ) were twofold greater during PR than with SS at 1 Hz. This difference was 1) abolished by inhibition of sarcoplasmic reticulum (SR) Ca accumulation by thapsigargin or caffeine; 2) greater at higher stimulation frequency and extracellular [Ca], which affected only SS τ; 3) abolished by the protein phosphatase inhibitor okadaic acid (10 μM, which selectively accelerated [Ca](i) decline during PR); 4) still present during stimulation or inhibition of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) by 10 μM forskolin or 1 μM H-89, respectively (SS and PR T values were abbreviated and prolonged, respectively); and 5) suppressed by 10 μM KN-62, a selective inhibitor of CaMKII, which selectively prolonged [Ca](i) decline during SS twitches. Both protein kinase inhibitors were also shown to decrease the SR Ca-uptake rate in digitonin-permeabilized rat myocytes. We conclude that CaMKII plays a major role in modulation of relaxation in rat ventricular myocytes, enhancing SR Ca uptake in a activity- dependent fashion. Our results are also compatible with a background, activity-independent stimulation of SR Ca uptake by PKA in intact rat myocytes.
AB - We investigated the role of Ca/calmodulin-dependent protein kinase (CaMKII) in relaxation and cytosolic free [Ca] ([Ca](i)) decline during steady-state (SS) and postrest (PR) twitches in intact rat ventricular myocytes. Half-time of mechanical relaxation and time constant of [Ca](i) decline (τ) were twofold greater during PR than with SS at 1 Hz. This difference was 1) abolished by inhibition of sarcoplasmic reticulum (SR) Ca accumulation by thapsigargin or caffeine; 2) greater at higher stimulation frequency and extracellular [Ca], which affected only SS τ; 3) abolished by the protein phosphatase inhibitor okadaic acid (10 μM, which selectively accelerated [Ca](i) decline during PR); 4) still present during stimulation or inhibition of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) by 10 μM forskolin or 1 μM H-89, respectively (SS and PR T values were abbreviated and prolonged, respectively); and 5) suppressed by 10 μM KN-62, a selective inhibitor of CaMKII, which selectively prolonged [Ca](i) decline during SS twitches. Both protein kinase inhibitors were also shown to decrease the SR Ca-uptake rate in digitonin-permeabilized rat myocytes. We conclude that CaMKII plays a major role in modulation of relaxation in rat ventricular myocytes, enhancing SR Ca uptake in a activity- dependent fashion. Our results are also compatible with a background, activity-independent stimulation of SR Ca uptake by PKA in intact rat myocytes.
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UR - http://www.scopus.com/inward/citedby.url?scp=0028930629&partnerID=8YFLogxK
M3 - Article
C2 - 7864197
AN - SCOPUS:0028930629
VL - 268
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 2 37-2
ER -