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Molecular identity of exosomal BK channels

Award Number: R01HL157453
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/24/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Molecular identity of exosomal BK channels - Abstract Extracellular vesicles (EVs) have gained significant attention since their discovery in 1983 as important mediators of intercellular communications, potential disease markers, therapeutic targets, and drug delivery vehicles. Though it is widely accepted that EVs get packaged inside the cell, pass through the extracellular environment, and deliver the cargo to the target cells. However, even after 37 yrs it is not determined, 1) how EVs handle the differential ionic environment (cytoplasm vs extracellular), 2) whether EVs possess any functional ion channels, and 3) whether any of these channels play a physiological role. We focused on answering these questions and focused on an ion with the largest gradient, i.e., potassium. Using the in silico approach, we discovered several ion channels, and the most prominent ion channels, we discovered in exosomes is BK. We incorporated a novel electrophysiology approach, near field electrophysiology, as canonical patch-clamp methods are not feasible due to the size of exosomes. We discovered that functional BK channels exist in exosomes, and decide the integrity of exosomes. Our preliminary data also indicate that exosomal BK can protect the heart from ischemia-reperfusion injury. We will now test the hypothesis that exosomes containing BK determine the content of exosomes, facilitate their survival in variable ionic environments, and protect the heart from IR injury. Overall the data supports the above hypothesis which will be tested using multiple approaches and pursuing the following specific aims to, 1. establish a presence, molecular identity, and biophysical properties of BK in exosomes, 2. determine the physiological role of BK in exosomes., and 3. elucidate the mechanistic role of exosomal BK channels in cardioprotection. In our proposal, we have incorporated genetic mice models, and innovative as well as a novel technology to understand a very basic and broad biological question. The outcome of this program will open an opportunity to study exosomal ion channels including BK channels, and advance the exosome field by determining how exosome survive variable osmolarities, establishing the molecular identity of exosomal ion channels, understand how cargo content is regulated by exosomal ion channels, and the role and mechanism of exosomal ion channels in cardioprotection. In the future, our study will set the ground for exploring other ion channels in exosomes from different living beings as well as organ systems.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $582,816 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	5	4/21/2026	NON-COMPETING CONTINUATION	$582,816
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	5	9/2/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $582,816

Issue Date FY: 2025 ( Subtotal = $602,584 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	4	11/13/2024	NON-COMPETING CONTINUATION	$542,326
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	4	8/12/2025	NON-COMPETING CONTINUATION	$60,258
														Subtotal = $602,584

Issue Date FY: 2024 ( Subtotal = $598,251 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	3	6/24/2024	NON-COMPETING CONTINUATION	$48,837
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	3	11/13/2023	NON-COMPETING CONTINUATION	$549,414
														Subtotal = $598,251

Issue Date FY: 2023 ( Subtotal = $618,334 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	2	11/17/2022	NON-COMPETING CONTINUATION	$556,501
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	2	3/10/2023	NON-COMPETING CONTINUATION	$61,833
														Subtotal = $618,334

Issue Date FY: 2022 ( Subtotal = $626,209 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	1	12/24/2021	NEW	$626,209
														Subtotal = $626,209

Grand Total All Awards = $3,028,194

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Molecular identity of exosomal BK channels

Award Number: R01HL157453

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/24/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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