SLMAP-3 is downregulated in human dilated ventricles and its overexpression promotes cardiomyocyte response to adrenergic stimuli by increasing intracellular calcium

2019 ◽  
Vol 97 (7) ◽  
pp. 623-630 ◽  
Author(s):  
Moni Nader ◽  
Ebtehal Alsolme ◽  
Shahd Alotaibi ◽  
Rahmah Alsomali ◽  
Dana Bakheet ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Intracellular Calcium ◽  
Cardiac Failure ◽  
Calcium Transient ◽  
Contraction Rate ◽  
Intracellular Calcium Transient ◽  
Viral Particles ◽  
Cardiac Myoblasts ◽  
Positive Chronotropic Effect

Structural dilation of cardiomyocytes (CMs) imposes a decline in cardiac performance that precipitates cardiac failure and sudden death. Since membrane proteins are implicated in dilated cardiomyopathy and heart failure, we evaluated the expression of the sarcolemmal membrane-associated protein (SLMAP) in dilated cardiomyopathy and its effect on CM contraction. We found that all 3 SLMAP isoforms (SLMAP-1, -2, and -3) are expressed in CMs and are downregulated in human dilated ventricles. Knockdown of SLMAPs in cultured CMs transduced with recombinant adeno-associated viral particles releasing SLMAP-shRNA precipitated reduced spontaneous contractile rate that was not fully recovered in SLMAP-depleted CMs challenged with isoproterenol (ISO), thus phenotypically mimicking heart failure performance. Interestingly, the overexpression of the SLMAP-3 full-length isoform induced a positive chronotropic effect in CMs that was more pronounced in response to ISO insult (vs. ISO-treated naïve CMs). Confocal live imaging showed that H9c2 cardiac myoblasts overexpressing SLMAP-3 exhibit a higher intracellular calcium transient peak when treated with ISO (vs. ISO-treated cells carrying a control adeno-associated viral particle). Proteomics revealed that SLMAP-3 interacts with the regulator of CM contraction, striatin. Collectively, our data demonstrate that SLMAP-3 is a novel regulator of CM contraction rate and their response to adrenergic stimuli. Loss of SLMAPs phenotypically mimics cardiac failure and crystallizes SLMAPs as predictive of dilated cardiomyopathy and heart failure.

Caffeine attenuates contraction-induced diminutions of the intracellular calcium transient in mouse lumbrical muscle ex vivo

2019 ◽  
Vol 97 (5) ◽  
pp. 429-435 ◽  
Author(s):  
Ian C. Smith ◽  
Rene Vandenboom ◽  
A. Russell Tupling
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Ex Vivo ◽  
Calcium Transient ◽  
Calcium Transients ◽  
Inotropic Effects ◽  
Intracellular Calcium Transient ◽  
Lumbrical Muscle ◽  
Lumbrical Muscles

The amount of calcium released from the sarcoplasmic reticulum in skeletal muscle rapidly declines during repeated twitch contractions. In this study, we test the hypothesis that caffeine can mitigate these contraction-induced declines in calcium release. Lumbrical muscles were isolated from male C57BL/6 mice and loaded with the calcium-sensitive indicator, AM-furaptra. Muscles were then stimulated at 8 Hz for 2.0 s in the presence or absence of 0.5 mM caffeine, at either 30 °C or 37 °C. The amplitude and area of the furaptra-based intracellular calcium transients and force produced during twitch contractions were calculated. For each of these measures, the values for twitch 16 relative to twitch 1 were higher in the presence of caffeine than in the absence of caffeine at both temperatures. We conclude that caffeine can attenuate contraction-induced diminutions of calcium release during repeated twitch contractions, thereby contributing to the inotropic effects of caffeine.

scholarly journals Pseudo-Noncompetitive Antagonism of BQ123 in Human ETA Endothelin Receptor-Mediated Intracellular Calcium Transient.

1993 ◽  
Vol 61 ◽  
pp. 70
Author(s):  
Aiji Sakamoto ◽  
Masashi Yanagisawa ◽  
Kazuwa Nakao ◽  
Teruhiko Toyo-oka ◽  
Mitsuo Yano ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Transient ◽  
Endothelin Receptor ◽  
Intracellular Calcium Transient

Initial Contractile Response of Isolated Rat Heart Cells to Halothane, Enflurane, and Isoflurane

1997 ◽  
Vol 86 (1) ◽  
pp. 137-146 ◽  
Author(s):  
David M. Wheeler ◽  
Todd R. Rice ◽  
William H. duBell ◽  
Harold A. Spurgeon
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Intracellular Calcium ◽  
Calcium Content ◽  
Calcium Transient ◽  
Temporary Increase ◽  
Heart Cells ◽  
Patch Clamp Technique ◽  
Intracellular Calcium Transient ◽  
Sarcoplasmic Reticulum Calcium ◽  
In Cells

Background In several beating cardiac muscle preparations, a short-lived increase in twitch tension or amplitude has been observed when they were exposed abruptly to solutions containing halothane or enflurane. As exposure to the anesthetics was continued, the expected negative inotropic effect became evident after the short-lived increase in twitch. No such increase in twitch has been reported during exposure to isoflurane. It has been hypothesized that this short-lived increase in twitch is caused by an enhancement of calcium release from the sarcoplasmic reticulum, but other mechanisms have not been excluded. Methods Freshly isolated, single rat ventricular cells were stimulated to beat at room temperature and abruptly exposed to solutions containing halothane (0.25-0.64 mM), enflurane (0.69-1 mM), or isoflurane (0.31-0.54 mM). During these exposures, twitch amplitude was measured and intracellular calcium concentration was followed using the calcium-sensitive dye indo-1. In some experiments, the whole-cell patch-clamp technique was used to measure membrane current. In addition, in several cells the sarcoplasmic reticulum calcium content was assessed through the response to brief pulses of caffeine. Results Both the twitch amplitude and the intracellular calcium transient were increased temporarily in cells abruptly exposed to halothane or enflurane. No such behavior was found with isoflurane. After continued exposure to all three agents, both the twitch amplitude and the calcium transient were less than control. During the beats exhibiting an increase in twitch, no alteration in the relation between cell length (twitch amplitude) and the intracellular calcium transient was found compared with control conditions. In addition, the temporary increase in twitch amplitude occurred in cells contracting under voltage-clamp control when halothane was introduced, and it was not associated with any increase in the calcium current. The sarcoplasmic reticulum calcium content at the time of the halothane-induced increase in twitch also was not increased. Conclusions The short-lived increase in twitch after abrupt exposure to halothane or enflurane is related to increased intracellular calcium during the beat and not to any changes in myofilament sensitivity to calcium. Because these results eliminate most alternative explanations for this phenomenon, the authors conclude that halothane, and probably also enflurane, increases the fraction of calcium released from the sarcoplasmic reticulum with each heart beat. Isoflurane appears to lack this action.

Contrasting effects of ischemia on the kinetics of membrane voltage and intracellular calcium transient underlie electrical alternans

2005 ◽  
Vol 288 (1) ◽  
pp. H400-H407 ◽  
Author(s):  
Vikram Lakireddy ◽  
Paramdeep Baweja ◽  
Asma Syed ◽  
Gil Bub ◽  
Mohamed Boutjdir ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Transient ◽  
Ischemic Heart ◽  
Membrane Voltage ◽  
Similar Degree ◽  
Electrical Instability ◽  
Dispersion Of Repolarization ◽  
Intracellular Calcium Transient ◽  
Photodiode Arrays ◽  
Kinetics Of

Repolarization alternans has been considered a strong marker of electrical instability. The objective of this study was to investigate the hypothesis that ischemia-induced contrasting effects on the kinetics of membrane voltage and intracellular calcium transient (CaiT) can explain the vulnerability of the ischemic heart to repolarization alternans. Ischemia-induced changes in action potential (AP) and CaiT resulting in alternans were investigated in perfused Langendorff guinea pig hearts subjected to 10–15 min of global no-flow ischemia followed by 10–15 min of reperfusion. The heart was stained with 100 μl of rhod-2 AM and 25 μl of RH-237, and AP and CaiT were simultaneously recorded with an optical mapping system of two 16 × 16 photodiode arrays. Ischemia was associated with shortening of AP duration (D) but delayed upstroke, broadening of peak, and slowed decay of CaiT resulting in a significant increase of CaiT-D. The changes in APD were spatially heterogeneous in contrast to a more spatially homogeneous lengthening of CaiT-D. CaiT alternans could be consistently induced with the introduction of a shorter cycle when the upstroke of the AP occurred before complete relaxation of the previous CaiT and generated a reduced CaiT. However, alternans of CaiT was not necessarily associated with alternans of APD, and this was correlated with the degree of spatially heterogeneous shortening of APD. Sites with less shortening of APD developed alternans of both CaiT and APD, whereas sites with greater shortening of APD could develop a similar degree of CaiT alternans but slight or no APD alternans. This resulted in significant spatial dispersion of APD. The study shows that the contrasting effects of ischemia on the duration of AP and CaiT and, in particular, on their spatial distribution explain the vulnerability of ischemic heart to alternans and the increased dispersion of repolarization during alternans.

Sign in / Sign up

Export Citation Format

Share Document