The voltage-gated sodium channel Na_v1.7 is a key regulator of pain signaling. Mutations in this channel can cause severe inherited pain syndromes or complete insensitivity to pain, making it a target for new analgesics.

Despite years of research, no selective Na_v1.7 modulator has reached the clinic. One major challenge is the lack of reliable preclinical assays that capture the state-dependent behavior of these channels.

In a new study, researchers from the University of Bari tested the effect of mexiletine, a non-selective sodium channel blocker used in neuropathic pain, on Na_v1.7 in two cell systems:

• TE671 cells (endogenously expressing Na_v1.7 )

• HEK293 cells (stably expressing human Na_v1.7 )

Using an automated patch clamp system (Patchliner), the team compared drug effects under voltage-, tonic-, and use-dependent conditions.

Key findings:

• Mexiletine blocked Na_v1.7 currents with almost identical potency in both models.

• The drug showed stronger effects when channels were inactivated (at depolarized potentials or high-frequency stimulation).

• Both cell lines had similar activation and inactivation properties.

• Mexiletine shifted inactivation to more negative voltages in a dose-dependent way.

Importantly, TE671 cells proved to be a robust alternative to engineered HEK293 systems. They are easier to handle and provide consistent results, making them valuable for drug screening.

This study confirms the utility of automated patch clamp for Na_v1.7 pharmacology and establishes mexiletine as a reference compound for future efforts to design selective modulators for pain therapy.

—

📖 Read the full article: Towards development of Nav1.7 channel modulators for pain treatment: A comparison of mexiletine effect in two cell models by automated patch clamp (Biomedicine & Pharmacotherapy, 2025)

🔬 Learn about the Patchliner