Work

Dynamic current-clamp unveiling the indispensable interplay between Nav1.7 and Nav1.8 for shaping action potential trajectory and retaining neuroexcitation of visceral sensory neurons

Year: 2025

Type: article

Abstract: Tetrodotoxin (TTX)-sensitive/Nav1.7- and TTX-resistive/Nav1.8 Na + channels contribute to neuroexcitation in the sensory neurons of the nodose ganglion (NG); however, their specific roles remain debatable. Therefore, we aimed to study the action potential (AP) elicited from NG neurons isolated from adult rats and simulated by a dynamic current clamp (DCC) using gNa0/Nav1.7 and/or gNa1/Nav1.8 injection. We trained and tuned the voltage-dependent profiles of the Na + current generated from the DCC using the Hodgkin–Huxley/Vandenberg models to match the AP parameters elicited by a brief pulse. A- or C-type AP could be simulated using DCC by applying gNa0 or gNa0/gNa1 alongside reduced gNa0 to avoid overshooting the up-stroke. This indicates the indispensability of these two Na + channels for shaping the AP trajectory with tight orchestration. The hump over the repolarization period featuring C-type neurons could be generated using DCC by adding gNa1 in this cellular model. Furthermore, both A- and C-type repeated discharges can be simulated using gNa0 or gNa1 with a reduced gNa0. Similar experiments were performed on human embryonic kidney 293 cells with stable Nav1.7 expression to mimic A-type-like conditions for further verification. Both A- and C-type-like APs were simulated in this expression system by adding gNa0 or gNa0/gNa1. Therefore, Nav1.7/Nav1.8 is crucial in shaping the AP trajectory, with specific timing for Nav1.8 activation to retain neuroexcitation in the sensory nervous system. Additionally, this pilot study will establish a fundamental base for the pharmacological screening of targeted ion channels and validate the disease-based mechanism in cardiology and neuroscience.

Source: Neuroscience Letters

DOI: 10.1016/j.neulet.2025.138387

Authors: Ying Li, Chen Zhang, Limin Han, Zhao Qian

Institutions: Harbin Medical University, Fourth Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Harbin Medical University

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funder: Heilongjiang Provincial Postdoctoral Science Foundation