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Bradshaw et al. Vessel Plus 2023;7:35 https://dx.doi.org/10.20517/2574-1209.2023.121 Page 15 of 21

Identification of the potential components of K channels and their roles in cardioprotection and
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neuroprotection, as well as non-channel mechanisms of action of pharmacologic channel openers, will
require ongoing investigation. The latest work on the components of K channels in cardioprotection
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[59]
found that two specific subunits - ROMK and SUR1 - are not implicated in myocardial protection . The
subunits implicated in cardioprotection and neuroprotection remain to be determined. Answering this
could lead to specific and targeted methods to exploit this channel pharmacologically to protect both the
heart and the brain during cardiac surgery.

SUMMARY
This article reviews the background of K channels in the context of their potential use for myocardial
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protection and neuroprotection, summarizes recent data supporting their use, and outlines future directions
for the role of these agents in cardiac surgery. Since it was first understood that K channels were present
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in cardiac cells and that they mimic IPC, research has advanced towards the goal of developing
pharmacologic agents that could target these channels to improve outcomes for patients after cardiac
surgery. Progress has been made using: genetic deletion to characterize the potential implicated protein
subunits of the involved channels; pharmacological research and single cell voltage clamping to differentiate
agents that result in channel activation; translational animal studies to demonstrate feasibility, safety, and
potential benefit and small human randomized trials to demonstrate feasibility. Recently, efforts have
focused specifically on a diazoxide because of its specificity for mitoK channels, and this agent shows
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promise for being able to facilitate cardioprotection and neuroprotection for patients. Continued
investigation of K channels and their precise molecular mechanism of action will lead and support a
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broader understanding of the potential ways to target these channels to improve the lives of human patients.

DECLARATIONS
Acknowledgments
We thank Dr. Mary Ann Wilson for her contribution to Figure 5 and for her permission to use this figure.

Author’s contributions
Literature review, writing, and editing of the manuscript: Bradshaw A
Literature review, writing, and editing, the conceptualization and critical analysis of the review: Lawton JS

Availability of data and materials
Not applicable

Financial support and sponsorship
None.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable

Consent for publication
Not applicable

Copyright
© The Author(s) 2023.