CaMKII is responsible for activity-dependent acceleration of relaxation in rat ventricular myocytes

R. A. Bassani, A. Mattiazzi, Donald M Bers

Research output: Contribution to journalArticle

106 Citations (Scopus)

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 languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume268
Issue number2 37-2
StatePublished - 1995
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
sarcoplasmic reticulum
Sarcoplasmic Reticulum
protein kinases
myocytes
Muscle Cells
KN 62
rats
uptake mechanisms
digitonin
Digitonin
okadaic acid
Okadaic Acid
Calcium-Calmodulin-Dependent Protein Kinases
forskolin
Thapsigargin
cyclic AMP
calmodulin
Colforsin
Protein Kinase Inhibitors

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

@article{1ce667001df84f98a0719a86600073ca,
title = "CaMKII is responsible for activity-dependent acceleration of relaxation in rat ventricular myocytes",
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.",
author = "Bassani, {R. A.} and A. Mattiazzi and Bers, {Donald M}",
year = "1995",
language = "English (US)",
volume = "268",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "2 37-2",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0028930629&partnerID=8YFLogxK

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 -