What is the clinical evidence from this study?

Study design: Review. Intervention: Telmisartan.

What does this research mean for the field?

In addition to its primary role as an AT1 receptor blocker, telmisartan enhances voltage-gated sodium currents (INa), thereby modulating action potential firing and cellular excitability in a variety of excitable cells. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This review aims to detail how telmisartan influences voltage-gated sodium currents and action potential firing behavior.

June 4, 2026Open Access

Telmisartan-Induced Alteration of Voltage-Gated Na+ Currents: Integrated Experimental and In Silico Approaches

Key Result

Telmisartan enhances voltage-gated Na+ currents and modulates action potential firing in excitable cells, according to integrated experimental and in silico models.

Key Points

This review aims to detail how telmisartan influences voltage-gated sodium currents and action potential firing behavior.
Overview of telmisartan's effects on INa across various cell types including neurons and cardiomyocytes.
Application of bifurcation analysis in modeled interneurons to assess telmisartan’s effects on subthreshold oscillations and spiking behavior.
Mathematical modeling using the Hodgkin-Huxley framework and molecular docking predictions to investigate telmisartan's interactions with NaV channels.
Telmisartan affects both peak and late components of INa, demonstrating differential effects on action potential dynamics.
Increased peak amplitude of INa and altered inactivation time course observed through modeling, indicating enhanced cellular excitability.
Potential for direct action on NaV channels alongside its role as an AT1 blocker, affecting various excitable cell types.

Structured PICO

Population

Various cell types (mHippoE-14 hippocampal neuron, cultured dorsal root ganglion neurons, HL-1 atrial cardiomyocytes) and in silico models (parvalbumin-expressing interneuron-based modeled cell, Hodgkin-Huxley model, Markovian process model)

Exposure

Telmisartan

Outcome

Modulation of voltage-gated Na+ current (INa) and action potential (AP) firing behaviorsurrogate

Telmisartan may directly enhance voltage-gated Na+ currents and modulate action potential firing in excitable cells, independent of its AT1 receptor antagonism.

Limitations

The mechanism of telmisartan's modulatory impact on NaV channel activity, whether direct or indirect, remains under investigation.

Abstract

Telmisartan (TEL) is a non-peptide, orally administered antihypertensive agent primarily known as angiotensin II type 1 (AT1) blocker. In this review, we provide a detailed overview of how TEL modulates voltage-gated Na+ current (INa) and affects action potential (AP) firing behavior. TEL exerts differential stimulatory effects on the peak and late components of INa when subjected to brief depolarizing pulses across a range of cell types, such as mHippoE-14 hippocampal neuron, cultured dorsal root ganglion neurons, and HL-1 atrial cardiomyocytes. TEL can augment the non-inactivating (persistent) INa elicited by ascending long ramp pulse in mHippoE-14 cells. By using a parvalbumin-expressing interneuron-based modeled cell combined with bifurcation analysis, it is possible to predict how applied current influences subthreshold oscillations and the generation of somatic spiking in the presence of TEL. According to the Hodgkin-Huxley model, mimicking the action of TEL—characterized by an increased peak amplitude of INa and a slowed inactivation time course—leads to the emergence of periodic oscillations in membrane potential. Using a Markovian process, a separate model can also be mathematically constructed, showing that changes in certain rate constants can simulate the effect of TEL on INa in cardiac cells. The molecular docking prediction between TEL and the NaV1.7 channel was made by expected formation of hydrophobic interactions as well as hydrogen bonding. In addition to its antagonistic action at the AT1 receptor and its agonistic activation of peroxisome proliferator-activator-γ, TEL may also directly enhance INa, thereby modulating AP firing in a variety of excitable cells. Current evidence supports TEL’s modulatory impact on NaV channel activity and cellular excitability, while also acknowledging that the mechanism—whether direct or indirect—remains under investigation.