Functional large-conductance calcium and voltage-gated potassium channels in extracellular vesicles act as gatekeepers of structural and functional integrity

Shridhar Sanghvi, Divya Sridharan, Parker Evans, Julie Dougherty, Kalina Szteyn, Denis Gabrilovich, Mayukha Dyta, Jessica Weist, Sandrine V. Pierre, Shubha Gururaja Rao, Dan R. Halm, Tingting Chen, Panagiotis S. Athanasopoulos, Amalia M. Dolga, Lianbo Yu, Mahmood Khan () and Harpreet Singh ()
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Shridhar Sanghvi: The Ohio State University
Divya Sridharan: The Ohio State University Wexner Medical Center
Parker Evans: The Ohio State University
Julie Dougherty: The Ohio State University Wexner Medical Center
Kalina Szteyn: The Ohio State University Wexner Medical Center
Denis Gabrilovich: The Ohio State University
Mayukha Dyta: The Ohio State University Wexner Medical Center
Jessica Weist: The Ohio State University Wexner Medical Center
Sandrine V. Pierre: Marshall University
Shubha Gururaja Rao: Ohio Northern University
Dan R. Halm: Wright State University
Tingting Chen: University of Groningen
Panagiotis S. Athanasopoulos: University of Groningen
Amalia M. Dolga: University of Groningen
Lianbo Yu: The Ohio State University
Mahmood Khan: The Ohio State University Wexner Medical Center
Harpreet Singh: The Ohio State University

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Extracellular vesicles (EVs) are associated with intercellular communications, immune responses, viral pathogenicity, cardiovascular diseases, neurological disorders, and cancer progression. EVs deliver proteins, metabolites, and nucleic acids into recipient cells to effectively alter their physiological and biological response. During their transportation from the donor to the recipient cell EVs face differential ionic concentrations, which can be detrimental to their integrity and impact their cargo content. EVs are known to possess ion channels and transporters in their membrane but neither the function nor the role of these channels in EVs is known. In this study, we discover a functional calcium-activated large-conductance potassium channel (BKCa) in the membrane of EVs. Furthermore, we establish that BKCa is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BKCa in functioning as gatekeepers and maintaining EV-mediated signaling.

Date: 2025
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DOI: 10.1038/s41467-024-55379-4

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