Disruption of Cellular Calcium Homeostasis

2007 ◽  
pp. 177-184
Keyword(s):  
Calcium Homeostasis ◽  
Cellular Calcium

Analysis of cellular calcium fluxes in cardiac muscle to understand calcium homeostasis in the heart

Cell Calcium ◽  
2007 ◽  
Vol 42 (4-5) ◽  
pp. 503-512 ◽  
Author(s):  
K DIBB ◽  
H GRAHAM ◽  
L VENETUCCI ◽  
D EISNER ◽  
A TRAFFORD
Keyword(s):  
Cardiac Muscle ◽  
Calcium Homeostasis ◽  
Calcium Fluxes ◽  
Cellular Calcium

scholarly journals Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content

2007 ◽  
Vol 102 (4) ◽  
pp. 1264-1275 ◽  
Author(s):  
Runa Hamid ◽  
Ellen Kilger ◽  
Michael Willem ◽  
Neville Vassallo ◽  
Markus Kostka ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Calcium Homeostasis ◽  
Precursor Protein ◽  
Atp Content ◽  
Intracellular Domain ◽  
Cellular Calcium

Abstract P467: Cardiac-specific Deletion Of Voltage Dependent Anion Channel 2 Leads To Dilated Cardiomyopathy By Altering Calcium Homeostasis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Thirupura S Shankar ◽  
Dinesh Kumar Anandamurugan Ramadurai ◽  
Kira Steinhorst ◽  
Salah Sommakia ◽  
Rachit Badolia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Calcium Signaling ◽  
Calcium Homeostasis ◽  
Calcium Uptake ◽  
Mitochondrial Calcium ◽  
Voltage Dependent Anion Channel ◽  
Knock Out ◽  
Cellular Calcium ◽  
Mitochondrial Calcium Uptake

Voltage dependent anion channel 2 (VDAC2) is a mitochondrial outer membrane porin known to play a significant role in apoptosis and calcium signaling. Abnormalities in cellular calcium homeostasis often leads to electrical and contractile dysfunction and can cause dilated cardiomyopathy and heart failure. Previous literature suggests that improving mitochondrial calcium uptake via VDAC2 rescues arrhythmia phenotypes in genetic models of impaired cellular calcium signaling. However, the direct role of VDAC2 in intracellular calcium signaling and cardiac function is not well understood. To elucidate the role of VDAC2 in calcium homeostasis, we generated a cardiac-specific deletion of Vdac2 in mice. Our results indicate that loss of VDAC2 in the myocardium during development causes severe impairment in excitation-contraction coupling by reducing mitochondrial calcium uptake (n=3, p<0.05) and thereby impairing intracellular calcium signaling. VDAC2 knock-out mice showed a significant reduction in RYR-mediated calcium release (F/F 0 ) and rate of calcium uptake by SERCA2a [tau(msec)] compared to control mice (N=3, WT=54, KO=38, p<0.0001 (F/F 0 ) and p<0.05 (tau)). We also observed adverse cardiac remodeling which progressed to severe dilated cardiomyopathy and death (N=6, p<0.0001). Reintroducing VDAC2 in 6-week-old knock-out mice partially rescued the cardiomyopathy phenotype evident from improvement in ejection fraction and fractional shortening (n=3, p<0.05). Improving mitochondrial calcium uptake via VDAC2 using a VDAC2 agonist efsevin, increased cardiac contractile force in a mouse model of pressure-overload induced heart failure (N=8, n=22, p<0.05). In conclusion, our findings demonstrate that VDAC2 plays a crucial role in cardiac function by influencing mitochondrial and cellular calcium signaling. Through this role in cellular calcium dynamics and excitation-contraction coupling VDAC2 emerges as a plausible therapeutic target for heart failure.

Sign in / Sign up

Export Citation Format

Share Document