Faradaic Pixels for Precise Hydrogen Peroxide Delivery to Control M‐Type Voltage‐Gated Potassium Channels

Abstract

H2O2 plays a significant role in a range of physiological processes where it performs vital tasks in redox signaling. The sensitivity of many biological pathways to H2O2 opens up a unique direction in the development of bioelectronics devices to control levels of reactive‐oxygen species (ROS). Here a microfabricated ROS modulation device that relies on controlled faradaic reactions is presented. A concentric pixel arrangement of a peroxide‐evolving cathode surrounded by an anode ring which decomposes the peroxide, resulting in localized peroxide delivery is reported. The conducting polymer (poly(3,4‐ethylenedioxythiophene) (PEDOT), is exploited as the cathode. PEDOT selectively catalyzes the oxygen reduction reaction resulting in the production of hydrogen peroxide (H2O2). Using electrochemical and optical assays, combined with modeling, the performance of the devices is benchmarked. The concentric pixels generate tunable gradients of peroxide and oxygen concentrations. The faradaic devices are prototyped by modulating human H2O2‐sensitive Kv7.2/7.3 (M‐type) channels expressed in a single‐cell model (Xenopus laevis oocytes). The Kv7 ion channel family is responsible for regulating neuronal excitability in the heart, brain, and smooth muscles, making it an ideal platform for faradaic ROS stimulation. The results demonstrate the potential of PEDOT to act as an H2O2 delivery system, paving the way to ROS‐based organic bioelectronics.

Redox regulation of Kv7 channels through EF3 hand of calmodulin

“…The redox response is characterized by a remarkable increase/recovery in M-current density on a second to minute time scale and it can be reversed by reducing agents (5, 10). This could derive from insertion of new channels, engaging silent channels, higher open probability, or a combination of these.…”

“…The generation of abnormally high levels of reactive oxygen species (ROS) is linked to cellular dysfunction, including neuronal toxicity and neurodegeneration (3)(4)(5).…”

“…A structure of the non-neuronal K V 7.1 subunit trapped in a non-functional conformation with the voltage-sensor disengaged from the pore suggests that the EF3hand of CaM may interact with the voltage-sensor (1,23,31) at a site essential for Mcurrent redox modulation (5,10). This 3D configuration has been assumed to confer a preferential use of EF3 during signaling on K V 7 channels (31)(32)(33)(34).…”

“…The generation of abnormally high levels of reactive oxygen species (ROS) is linked to cellular dysfunction, including neuronal toxicity and neurodegeneration (3-5). In addition, ROS are important mediators of normal cellular functions in multiple intracellular signal transduction pathways (6-9).…”

“…Augmentation of the M-current can be induced by an external H 2 O 2 concentration as low as 5 μM (10), or even in the nM range (5). The M-current flows through channels formed of neuronal K V 7 subunits (K V 7.2-K V 7.5, encoded by KCNQ 2-5 genes).…”