Reviews
Vol. 3 (2026)
Therapeutic target for reversal of overdose-induced respiratory depression: BK channels in the carotid body
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 5 June 2026
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Opioid-overdose has morphed from a mainly single-entity problem (e.g., heroin, or fentanyl, or some other opioid) to a predominantly polysubstance combination of opioid + non-opioid problem. Reversal of opioid-alone respiratory depression is straightforward (albeit not always easy) using an opioid receptor antagonist such as naloxone. Unfortunately, combinations containing non-opioid contributors to respiratory depression are not so pharmacologically straightforward. Given that the non-opioid component is often not known, a reversal agent that would work independently of the combination components (‘agnostic’) is highly desired. A promising target for such a drug is the peripherally-located carotid body, the primary peripheral arterial chemoreceptor that detects arterial hypoxia and responds with compensatory signals. Large-conductance Ca²⁺- and voltage-activated potassium channels (BK, Maxi-K, KCa1.1) within the glomus cells regulate the response of the carotid body to hypoxia, and the gain and stability of the respiratory feedback loop. Hypoxia inhibits BK channels via direct and indirect mechanisms, enhancing the gain of signaling from the carotid body to brainstem respiratory nuclei. Although initially proposed to be intrinsic oxygen sensors, current evidence supports a more integrative role in modulatory control of carotid body activity. This minireview gives a succinct overview of the molecular biology and structural diversity of BK channels and their accessory β/g subunits, the physiological mechanisms linking BK channel activity to hypoxia chemotransduction, and systems-level roles in negative-feedback drive of ventilatory responsiveness. Also included are future directions and a proposed control system model of carotid body BK feedback.
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How to Cite
1.
Raffa RB. Therapeutic target for reversal of overdose-induced respiratory depression: BK channels in the carotid body. Adv Health Res [Internet]. 2026 Jun. 5 [cited 2026 Jun. 27];3(1). Available from: https://www.ahr-journal.org/site/article/view/135
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