Air Pollution and Cardiac Arrhythmias: From Epidemiological and Clinical Evidences to Cellular Electrophysiological Mechanisms

Cardiovascular disease is the leading cause of death worldwide and kills over 17 million people per year. In the recent decade, growing epidemiological evidence links air pollution and cardiac arrhythmias, suggesting a detrimental influence of air pollution on cardiac electrophysiological functionality. However, the proarrhythmic mechanisms underlying the air pollution-induced cardiac arrhythmias are not fully understood. The purpose of this work is to provide recent advances in air pollution-induced arrhythmias with a comprehensive review of the literature on the common air pollutants and arrhythmias. Six common air pollutants of widespread concern are discussed, namely particulate matter, carbon monoxide, hydrogen sulfide, sulfur dioxide, nitrogen dioxide, and ozone. The epidemiological and clinical reports in recent years are reviewed by pollutant type, and the recently identified mechanisms including both the general pathways and the direct influences of air pollutants on the cellular electrophysiology are summarized. Particularly, this review focuses on the impaired ion channel functionality underlying the air pollution-induced arrhythmias. Alterations of ionic currents directly by the air pollutants, as well as the alterations mediated by intracellular signaling or other more general pathways are reviewed in this work. Finally, areas for future research are suggested to address several remaining scientific questions.

Calmodulin Interactions with Voltage-Gated Sodium Channels

Calmodulin (CaM) is a small protein that acts as a ubiquitous signal transducer and regulates neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. CaM modulates the voltage-gated sodium channel gating process, alters sodium current density, and regulates sodium channel protein trafficking and expression. Many mutations in the CaM-binding IQ domain give rise to diseases including epilepsy, autism, and arrhythmias by interfering with CaM interaction with the channel. In the present review, we discuss CaM interactions with the voltage-gated sodium channel and modulators involved in CaM regulation, as well as summarize CaM-binding IQ domain mutations associated with human diseases in the voltage-gated sodium channel family.

The murburn precepts for cellular electrophysiology

Based on murburn model of bioenergetics, we had recently proposed the rationale for cation distribution in cells (Manoj & Tamagawa, 2020) and also demonstrated a potential generation based on murzyme activity (Tamagawa et al., 2021). Herein, the precepts for murburn concept based electrophysiological phenomena- differentiation of ions at the interface, and action potential generation/conduction along a neuron are briefly charted. Contrary to the ionic theories that prevail, the murburn model is electronic; although, the contributions of ions are not discounted.

Remote nongenetic optical modulation of neuronal activity using fuzzy graphene

The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and between tissues and can enable therapeutic interventions.