scholarly journals Interplay between SERCA and sarcolemmal Ca2+efflux pathways controls spontaneous release of Ca2+from the sarcoplasmic reticulum in rat ventricular myocytes

2004 ◽  
Vol 559 (1) ◽  
pp. 121-128 ◽  
Author(s):  
S. C. O'Neill ◽  
L. Miller ◽  
R. Hinch ◽  
D. A. Eisner
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Spontaneous Release ◽  
Rat Ventricular Myocytes

Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes

1996 ◽  
Vol 270 (3) ◽  
pp. H907-H914 ◽  
Author(s):  
H. Terada ◽  
H. Hayashi ◽  
N. Noda ◽  
H. Satoh ◽  
H. Katoh ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Channel Blocker ◽  
Ventricular Myocytes ◽  
Inhibitory Effect ◽  
Antiarrhythmic Action ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Triggered Activity ◽  
Rat Ventricular Myocytes ◽  
High Concentrations

It has been shown that the occurrence of the transient inward current, which is responsible for triggered activity, was often associated with propagating regions of increased intracellular Ca2+ concentration ([Ca2+]i), i.e., the “Ca2+ wave.” To investigate the mechanism of antiarrhythmic action of Mg2+, we have studied effects of high concentrations of Mg2+ on Ca2+ waves in isolated rat ventricular myocytes. [Ca2+]i was estimated using the Ca(2+)-indicating probe indo 1. Ca2+ waves in myocytes, stimulated at 0.2 Hz, were induced by perfusion of isoproterenol (10(-7) M). High Mg2+ concentration suppressed Ca2+ waves in a concentration-dependent manner (36% at 4 mM, 70% at 8 mM, and 82% at 12 mM). The Ca2+ channel blocker verapamil also suppressed Ca2+ waves in a similar way. In contrast with marked depression of Ca2+ transients by verapamil, Ca2+ transients were not affected by high Mg2+ concentration (8 mM). High Mg2+ concentration also reduced frequencies of Ca2+ waves in the absence of electrical stimulation, whereas verapamil failed to reduce frequencies of Ca2+ waves. Reduction in frequency of Ca2+ waves by high Mg2+ concentration was associated with slowing of propagation velocity of Ca2+ waves. To examine whether suppressive effects of high Mg2+ concentration on Ca2+ waves were related to an increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of high-Mg2+ solution on [Mg2+]i was examined in myocytes loaded with mag-fura 2. An increase in extracellular Mg2+ concentration from 1 to 12 mM increased [Mg2+]i from 1.06 +/- 0.16 to 1.87 +/- 0.22 mM (P < 0.01) in 30 min. To examine the effect of high Mg2+ concentration on amount of releasable Ca2+ in the sarcoplasmic reticulum, the effect of high Mg2+ concentration on the Ca2+ transient induced by a rapid application of caffeine was examined. High-Mg2+ solution increased the peak of the caffeine-induced Ca2+ transient. These results suggest that the inhibitory effect of Mg2+ on Ca2+ waves was not due to inhibition of the sarcolemmal Ca2+ channel but could be due to a decreased propensity for the sarcoplasmic reticulum to divest itself of excess Ca2+.

Antagonistic Actions of Halothane and Sevoflurane on Spontaneous Ca2+Release in Rat Ventricular Myocytes

2006 ◽  
Vol 105 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Mark D. Graham ◽  
Philip M. Hopkins ◽  
Simon M. Harrison
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Positive Inotropic Effect ◽  
Ventricular Myocytes ◽  
Inotropic Effect ◽  
Release Process ◽  
Rat Ventricular Myocytes ◽  
Fura 2 ◽  
Threefold Increase ◽  
Subcellular Target ◽  
Isolated Rat

Background Halothane has been reported to sensitize Ca(2+) release from the sarcoplasmic reticulum (SR), which is thought to contribute to its initial positive inotropic effect. However, little is known about whether isoflurane or sevoflurane affect the SR Ca(2+) release process, which may contribute to the inotropic profile of these anesthetics. Methods Mild Ca(2+) overload was induced in isolated rat ventricular myocytes by increase of extracellular Ca(2+) to 2 mM. The resultant Ca(2+) transients due to spontaneous Ca(2+) release from the SR were detected optically (fura-2). Cells were exposed to 0.6 mM anesthetic for a period of 4 min, and the frequency and amplitude of spontaneous Ca(2+) transients were measured. Results Halothane caused a temporary threefold increase in frequency and decreased the amplitude (to 54% of control) of spontaneous Ca(2+) transients. Removal of halothane inhibited spontaneous Ca release before it returned to control. In contrast, sevoflurane initially inhibited frequency of Ca(2+) release (to 10% of control), whereas its removal induced a burst of spontaneous Ca(2+) release. Isoflurane had no significant effect on either frequency or amplitude of spontaneous Ca(2+) release on application or removal. Sevoflurane was able to ameliorate the effects of halothane on the frequency and amplitude of spontaneous Ca(2+) release both on application and wash-off. Conclusions Application of halothane and removal of sevoflurane sensitize the SR Ca(2+) release process (and vice versa on removal). Sevoflurane reversed the effects of halothane, suggesting they may act at the same subcellular target on the SR.

scholarly journals Changes of SERCA activity have only modest effects on sarcoplasmic reticulum Ca2+content in rat ventricular myocytes

2011 ◽  
Vol 589 (19) ◽  
pp. 4723-4729 ◽  
Author(s):  
E. F. Bode ◽  
S. J. Briston ◽  
C. L. Overend ◽  
S. C. O’Neill ◽  
A. W. Trafford ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Rat Ventricular Myocytes

Differential Effects of Fentanyl and Morphine on Intracellular Ca2+Transients and Contraction in Rat Ventricular Myocytes 

1998 ◽  
Vol 89 (6) ◽  
pp. 1532-1542 ◽  
Author(s):  
Noriaki Kanaya ◽  
Daniel R. Zakhary ◽  
Paul A. Murray ◽  
Derek S. Damron
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Myocardial Contractility ◽  
Ventricular Myocytes ◽  
Free Acid ◽  
Intact Cells ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Rat Ventricular Myocytes ◽  
Fura 2 ◽  
Cardiac Excitation

Background Our objective was to elucidate the direct effects of fentanyl and morphine on cardiac excitation-contraction coupling using individual, field-stimulated rat ventricular myocytes. Methods Freshly isolated myocytes were loaded with fura-2 and field stimulated (0.3 Hz) at 28 degrees C. Amplitude and timing of intracellular Ca2+ concentration (at a 340:380 ratio) and myocyte shortening (video edge detection) were monitored simultaneously in individual cells. Real time Ca2+ uptake into isolated sarcoplasmic reticulum vesicles was measured using fura-2 free acid in the extravesicular compartment. Results The authors studied 120 cells from 30 rat hearts. Fentanyl (30-1,000 nM) caused dose-dependent decreases in peak intracellular Ca2+ concentration and shortening, whereas morphine (3-100 microM) decreased shortening without a concomitant decrease in the Ca2+ transient. Fentanyl prolonged the time to peak and to 50% recovery for shortening and the Ca2+ transient, whereas morphine only prolonged the timing parameters for shortening. Morphine (100 microM), but not fentanyl (1 microM), decreased the amount of Ca2+ released from intracellular stores in response to caffeine in intact cells, and it inhibited the rate of Ca2+ uptake in isolated sarcoplasmic reticulum vesicles. Fentanyl and morphine both caused a downward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on the Ca2+ transient. Conclusions Fentanyl and morphine directly depress cardiac excitation-contraction coupling at the cellular level. Fentanyl depresses myocardial contractility by decreasing the availability of intracellular Ca2+ and myofilament Ca2+ sensitivity. In contrast, morphine depresses myocardial contractility primarily by decreasing myofilament Ca2+ sensitivity.

CaMKII-dependent reactivation of SR Ca2+ uptake and contractile recovery during intracellular acidosis

2002 ◽  
Vol 283 (1) ◽  
pp. H193-H203 ◽  
Author(s):  
Noriyuki Nomura ◽  
Hiroshi Satoh ◽  
Hajime Terada ◽  
Masaki Matsunaga ◽  
Hiroshi Watanabe ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Selective Inhibitor ◽  
Intracellular Acidosis ◽  
Rat Ventricular Myocytes ◽  
Calmodulin Kinase ◽  
Intracellular Ca ◽  
Contractile Recovery ◽  
Contractile Performance

In hearts, intracellular acidosis disturbs contractile performance by decreasing myofibrillar Ca2+ response, but contraction recovers at prolonged acidosis. We examined the mechanism and physiological implication of the contractile recovery during acidosis in rat ventricular myocytes. During the initial 4 min of acidosis, the twitch cell shortening decreased from 2.3 ± 0.3% of diastolic length to 0.2 ± 0.1% (means ± SE, P < 0.05, n = 14), but in nine of these cells, contractile function spontaneously recovered to 1.5 ± 0.3% at 10 min ( P < 0.05 vs. that at 4 min). During the depression phase, both the diastolic intracellular Ca2+ concentration ([Ca2+]i) and Ca2+ transient (CaT) amplitude increased, and the twitch [Ca2+]i decline prolonged significantly ( P < 0.05). In the cells that recovered, a further increase in CaT amplitude and a reacceleration of twitch [Ca2+]i decline were observed. The increase in diastolic [Ca2+]i was less extensive than the increase in the cells that did not recover ( n = 5). Blockade of sarcoplasmic reticulum (SR) function by ryanodine (10 μM) and thapsigargin (1 μM) or a selective inhibitor of Ca2+-calmodulin kinase II, 2-[ N- (2-hydroxyethyl)- N-(4-methoxybenzenesulfonyl)] amino- N-(4-chlorocinnamyl)- N-methyl benzylamine (1 μM) completely abolished the reacceleration of twitch [Ca2+]i decline and almost eliminated the contractile recovery. We concluded that during prolonged acidosis, Ca2+-calmodulin kinase II-dependent reactivation of SR Ca2+ uptake could increase SR Ca2+ content and CaT amplitude. This recovery can compensate for the decreased myofibrillar Ca2+ response, but may also cause Ca2+ overload after returning to physiological pHi.

Repletion of sarcoplasmic reticulum Ca after ryanodine in rat ventricular myocytes

1993 ◽  
Vol 265 (2) ◽  
pp. H604-H615 ◽  
Author(s):  
W. H. duBell ◽  
B. Lewartowski ◽  
H. A. Spurgeon ◽  
H. S. Silverman ◽  
E. G. Lakatta
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Positive Inotropic Effect ◽  
Ventricular Myocytes ◽  
High Rate ◽  
Resting Cells ◽  
Adrenergic Agonist ◽  
Rat Ventricular Myocytes ◽  
Contractile Activation ◽  
Beta Adrenergic Agonist ◽  
Pulse Stimulation

The ryanodine (R)-induced loss of sarcoplasmic reticulum (SR) Ca2+ and the abilities of the SR to accumulate Ca2+ and participate in contractile activation after R were studied in rat ventricular myocytes. Indo 1 fluorescence (IF) indexed cytosolic Ca2+, and caffeine assayed SR Ca2+. Before R, there was a negative staircase, and the SR accumulated Ca2+ at rest. During stimulation (0.5 Hz), R decreased IF and contraction, converting the negative staircase to positive. When R was pulsed onto resting cells, IF increased and cells shortened, subsequently behaving as if stimulated in R. After R, there was no caffeine-releasable Ca2+ at rest, and little accumulated during 0.5-Hz stimulation. At high rates, caffeine-releasable Ca2+ and diastolic IF increased. In isoproterenol and R, IF transients and contractions recovered at 0.5 Hz with a marked positive staircase and little diastolic IF increase. Within 10 beats, SR Ca2+ accumulated to pre-R levels. R eliminated the positive inotropic effect of paired-pulse stimulation, but isoproterenol temporarily restored it. Twitch contractions in thapsigargin, an SR Ca2+ pump blocker, and isoproterenol were slow compared with control or R + isoproterenol. R leaks SR Ca2+ into the cytosol. SR Ca2+ can be repleted in R by high-rate stimulation or by low-rate stimulation with a beta-adrenergic agonist. SR Ca2+ release in R can be temporarily restored if Ca2+ influx and SR Ca2+ pumping are increased enough to overcome the SR Ca2+ leak.

Sign in / Sign up

Export Citation Format

Share Document