Faculty Opinions recommendation of Differential redox regulation of ORAI ion channels: a mechanism to tune cellular calcium signaling.

Ion channels perform a variety of cellular functions in lung epithelia. Oxidant- and antioxidant-mediated mechanisms (that is, redox regulation) of ion channels are areas of intense research. Significant progress has been made in our understanding of redox regulation of ion channels since the last Experimental Biology report in 2003. Advancements include: 1) identification of nonphagocytic NADPH oxidases as sources of regulated reactive species (RS) production in epithelia, 2) an understanding that excessive treatment with antioxidants can result in greater oxidative stress, and 3) characterization of novel RS signaling pathways that converge upon ion channel regulation. These advancements, as discussed at the 2013 Experimental Biology Meeting in Boston, MA, impact our understanding of oxidative stress in the lung, and, in particular, illustrate that the redox state has profound effects on ion channel and cellular function.

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Calcium signaling of in situ chondrocytes in articular cartilage under compressive loading: Roles of calcium sources and cell membrane ion channels

Journal of Orthopaedic Research® ◽

10.1002/jor.23768 ◽

2017 ◽

Vol 36 (2) ◽

pp. 730-738 ◽

Cited By ~ 17

Author(s):

Mengxi Lv ◽

Yilu Zhou ◽

Xingyu Chen ◽

Lin Han ◽

Liyun Wang ◽

...

Keyword(s):

Articular Cartilage ◽

Ion Channels ◽

Cell Membrane ◽

Calcium Signaling ◽

Compressive Loading ◽

Calcium Sources

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Decision letter: Ion channels and calcium signaling in motile cilia

10.7554/elife.11066.014 ◽

2015 ◽

Keyword(s):

Ion Channels ◽

Calcium Signaling ◽

Motile Cilia

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Ion Channels and Calcium Signaling in the Microcirculation

10.1016/s1063-5823(20)x0002-0 ◽

2020 ◽

Keyword(s):

Ion Channels ◽

Calcium Signaling

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

Circulation Research ◽

10.1161/res.129.suppl_1.p467 ◽

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.

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