Modulatory Impact of Oxidative Stress on Action Potentials in Pathophysiological States: A Comprehensive Review

Abstract

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses, significantly affects cellular function and viability. It plays a pivotal role in modulating membrane potentials, particularly action potentials (APs), essential for properly functioning excitable cells such as neurons, smooth muscles, pancreatic beta cells, and myocytes. The interaction between oxidative stress and AP dynamics is crucial for understanding the pathophysiology of various conditions, including neurodegenerative diseases, cardiac arrhythmias, and ischemia-reperfusion injuries. This review explores how oxidative stress influences APs, focusing on alterations in ion channel biophysics, gap junction, calcium dynamics, mitochondria, and Interstitial Cells of Cajal functions. By integrating current research, we aim to elucidate how oxidative stress contributes to disease progression and discuss potential therapeutic interventions targeting this interaction.

Keywords: APs; biophysics; ion channel; oxidative stress; pathophysiology.

Figure 1

Illustration of the processes by which oxidative stress disrupts normal cells through the induction of reactive oxygen species. The red positive signs indicate ROS enhancers, while the red negative signs indicate ROS inhibitors. Oxidative stress radicals that modulate the shape of the cell are depicted by red stars and circles.

Figure 2

(a) Illustration of the simulated membrane depolarization (black solid line), AP (red solid line), depolarization phase, repolarization phase, threshold potential (star mark), and resting membrane potential, which is maintained at −52 mV. (b–d) show simulated cardiac AP, slow wave with a burst, and series of neuronal Aps, respectively. The X-axis represents unscaled time, while the Y-axis represents unscaled membrane potential.

Figure 3

(a) shows how connexins from Cell 1 and Cell 2 form a gap junction, enabling signal transfer between them, as indicated by the red bidirectional arrow. (b) depicts six cells connected in a linear arrangement through gap junctions (red arrow), illustrating signal transmission along this network. (c) is a schematic of the gap junction between Cell 1 and Cell 2, where V₁ and V₂ represent their membrane potentials, and r_j indicates the gap junction resistance.

Figure 4

A schematic representation of the ICC cell among smooth muscle cells (SM cells). An ICC cell consists of several ion channels and is connected to neighboring cells via a gap junction.

Figure 5

Illustrates Ca²⁺ dynamics processes with all cellular and sub-cellular compartments described in the previous paragraph.

Figure 6

Illustrates protein-mediating ion fluxes in the outer mitochondria membrane described in the previous paragraph. The putative channel acetylcholine receptor is also illustrated.

Figure 7

A schematic diagram of the representation of the redox modulation on membrane potential via several pathways that can modulate the AP parameter and cellular excitability.