The Cellular Battery: Rethinking the Electrochemical Basis of Transmembrane Potential

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Abstract

The origin of the transmembrane potential (TMP) in living cells is one of the foundational questions of cellular physiology. The dominant explanatory framework---the ion-pump model---attributes TMP to the active, \ATP-dependent displacement of ions (principally \Naplus\ and \Kplus) across the plasma membrane by dedicated protein complexes. This view, consolidated through the seminal work of Hodgkin and Huxley and the structural characterisation of the Na,K-ATPase, has shaped decades of research in neuroscience, cardiology, and cell biology. A competing framework, the \textit{murburn concept} developed by Manoj and colleagues, proposes a fundamentally different mechanism. According to this view, TMP is not the product of mechanical ion pumping but emerges spontaneously from asymmetric redox chemistry at the membrane interface. Diffusible reactive species (DRS), generated continuously during aerobic respiration, accumulate differentially on either side of the membrane, producing effective charge separation analogous to that observed in electrochemical cells. This perspective examines both frameworks critically, identifies the core points of disagreement, and evaluates the explanatory scope and empirical challenges of each. We argue that the murburn framework raises legitimate and underexplored questions about the thermodynamic sufficiency of the ion-pump model, and that a productive synthesis may lie in recognising redox chemistry as a primary contributor to membrane polarisation---rather than a secondary consequence of it.

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europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-22T02:00:06.705733+00:00
License: CC-BY-4.0