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Calibrating resting membrane potential
The 2020 paper starts from the view that resting membrane potential depends on membrane permeability and on the gradients of Na+, K+ and Cl−1. It used solutions with set ion concentrations and compared dye fluorescence with patch clamp readings. For MDA-MB-231 breast cancer cells, raising potassium and lowering sodium raised dye signal, and the slope was 1.28±0.11 F/mV3. The authors concluded that calibration curves differ between cell lines.
Signaling beyond neurons
The 2021 review, co-authored with Levin and others, asks how cells integrate over long distances before nerves, vessels and lymphatics exist. It calls this an open mystery for developmental biologists until recently4. It also lists long-range bioelectric phenomena whose mechanisms were still unknown, including the long-distance normalization of tumors and bioelectric repair of genetic teratogenesis5.
Laterality in breast cancer
The 2023 paper asks whether ion channel expression differs between left and right breast tumors. The authors built a six-gene ion channel signature. Its expression was lower in tumor than in normal tissue, and lower in left-sided than right-sided tumors6. In a discovery cohort, the signature correlated inversely with KI67 and with a stemness score7.
The RMP is determined by two main factors: (1) the membrane permeability and (2) concentration gradient of the most abundant permeable ions, Na+, K+, and Cl− (Fig. 1A).
Bonzanni M, Payne SL, Adelfio M, Kaplan DL, Levin M, Oudin…, 2020 · Defined extracellular ionic solutions to study and manipulate the cellular… · open at passage 4The slope of the resulting linear fit indicates the change in the fluorescence value per unit of voltage change (ΔF/ΔV), shown to be 1.76±0.19 F/mV for RPTECs.
Bonzanni M, Payne SL, Adelfio M, Kaplan DL, Levin M, Oudin…, 2020 · Defined extracellular ionic solutions to study and manipulate the cellular… · open at passage 11We find a tight correlation between the RMP measured by patch clamp and DiBAC intensity in MDA-MB-231 cells, with a change in the fluorescence value per unit of voltage change (ΔF/ΔV of 1.28±0.11 F/mV)
Bonzanni M, Payne SL, Adelfio M, Kaplan DL, Levin M, Oudin…, 2020 · Defined extracellular ionic solutions to study and manipulate the cellular… · open at passage 12Until recently, however, the mechanisms through which individual cells integrate over long distances, before these specialized communication channels have formed, have remained an open mystery for developmental biologists.
McMillen P, Oudin MJ, Levin M, Payne SL, 2021 · Beyond Neurons: Long Distance Communication in Development and Cancer · open at passage 4there remain several examples of long-range bioelectric phenomena, such as the long-distance normalization of tumors (Chernet and Levin, 2014), bioelectric repair of genetic teratogenesis (Pai et al., 2020)
McMillen P, Oudin MJ, Levin M, Payne SL, 2021 · Beyond Neurons: Long Distance Communication in Development and Cancer · open at passage 13And among the tumors, we found a decreased expression in L-sided compared to R-sided ones (Mann–Whitney test for non-normal data, p = 0.005, Supplementary File S3).
Masuelli S, Real S, McMillen P, Oudin M, Levin M, Roqué M, 2023 · The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left-Right… · open at passage 12In the Discovery Cohort, we observed a strong inverse correlation between the 6-ICH signature and both markers, (r = −0.47 and r = −0.62 respectively, Spearman correlation test, p < 0.0001)
Masuelli S, Real S, McMillen P, Oudin M, Levin M, Roqué M, 2023 · The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left-Right… · open at passage 15
2020
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2021
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2023
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