Abstract
Acidosis and its associated pathologies predispose patients to develop cardiac arrhythmias and even cardiac arrest. These arrhythmias are assumed to be the result of membrane depolarization, however, the exact mechanism of depolarization during acidosis is not well defined. In our study, the model of quantum tunneling of protons is used to explain the membrane depolarization that occurs during acidosis. It is found that protons can tunnel through closed activation and inactivation gates of voltage-gated sodium channels Nav1.5 that are present in the membrane of cardiac cells. The quantum tunneling of protons results in quantum conductance, which is evaluated to assess its effect on membrane potential. The quantum conductance of extracellular protons is higher than that of intracellular protons. This predicts an inward quantum current of protons through the closed sodium channels. Additionally, the values of quantum conductance are influential and can depolarize the membrane potential according to the quantum version of the GHK equation. The quantum mechanism of depolarization is distinct from other mechanisms because the quantum model suggests that protons can directly depolarize the membrane potential, and not only through indirect effects as proposed by other mechanisms in the literature. Understanding the pathophysiology of arrhythmias mediated by depolarization during acidosis is crucial to treat and control them and to improve the overall clinical outcomes of patients.
Highlights
In the human body, acid-base balance is under tight regulations because the function of cells requires normal plasma pH levels, and only a minimal disturbance in the blood acidity could affect cells significantly and render them unable to work
The model states that protons are able to pass through the closed voltage-gated sodium channels via quantum tunneling
According to the quantum model, quantum tunneling of protons results in a quantum current that passes through the channel and there will be a quantum conductance of single channel and quantum membrane conductance
Summary
Acid-base balance is under tight regulations because the function of cells requires normal plasma pH levels, and only a minimal disturbance in the blood acidity could affect cells significantly and render them unable to work. This offers a good opportunity to unveil why acidosis is arrhythmogenic in cardiac tissue from the quantum perspective and improve our understanding of the pathophysiology of acidosis-induced depolarization. Mutation in the S4 voltage sensor in the α subunit of Nav1.4 alters the channel properties and leads to a leak of sodium or protons through the voltage sensor causing depolarization [17] These currents are called gating pore currents (omega currents) that are not conducted through the usual pathway of conduction but conducted through voltage sensor domains as proposed in the literature [14,15,16,17]. The direct correlation between proton leak, membrane depolarization and cardiac arrhythmias supports the quantum model because it predicts that quantum tunneling of protons through closed gates can depolarize the membrane potential directly and cause arrhythmias, as will be discussed later in the study
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