Kv1.3 in the spotlight for treating immune diseases

ABSTRACT

Introduction

Kv1.3 is the main voltage-gated potassium channel of leukocytes from both the innate and adaptive immune systems. Channel function is required for common processes such as Ca²⁺ signaling but also for cell-specific events. In this context, alterations in Kv1.3 are associated with multiple immune disorders. Excessive channel activity correlates with numerous autoimmune diseases, while reduced currents result in increased cancer prevalence and immunodeficiencies.

Areas covered

This review offers a general view of the role of Kv1.3 in every type of leukocyte. Moreover, diseases stemming from dysregulations of the channel are detailed, as well as current advances in their therapeutic research.

Expert opinion

Kv1.3 arises as a potential immune target in a variety of diseases. Several lines of research focused on channel modulation have yielded positive results. However, among the great variety of specific channel blockers, only one has reached clinical trials. Future investigations should focus on developing simpler administration routes for channel inhibitors to facilitate their entrance into clinical trials. Prospective Kv1.3-based treatments will ensure powerful therapies while minimizing undesired side effects.

KEYWORDS:

• Kv1.3
• ion channels
• immune system
• pharmacology
• therapeutics

Article highlights

• Kv1.3 is the main voltage-gated potassium channel of leukocytes from innate and adaptive immunity.

• Kv1.3 participates in cell activation, proliferation, cytokine production and apoptosis, among other cellular processes.

• Alterations in Kv1.3 expression and/or activity correlate with immune disorders.

• Selective inhibition of the channel has improved the pathogenesis of immune diseases in preclinical trials.

• Only the Kv1.3 inhibitor dalazatide has reached early clinical trials with positive outcomes.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Authors thank the past members of the MP laboratory that have contributed to pushing forward the knowledge of the Kv1.3 biology. English language editing for this manuscript was performed by American Journal Experts.

Additional information

Funding

Supported by the Ministerio de Ciencia e Innovación (PID2020-112647RB-I00 and PID2023-148085OB-I00) and AEI (10.13039/501100011033), Spain and European Regional Development Fund (FEDER). J Capera is a Cancer Research Institute Irvington Fellow (CRI4503).