Beta1 subunits enable fentanyl-induced BK channel activation and opioid regulation of cerebral artery diameter.
- 1Department of Pharmacology, Addiction Science and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, USA.
- 2Department of Biochemistry, Faculty of Pharmacy Cairo University, Egypt.
Abstract
Ultra-potent synthetic opioids are powerful analgesics but also a leading cause of drug overdose deaths. Calcium-/voltage-gated potassium channels of large conductance (BK) control vital physiological processes, with their accessory β1 (encoded by Kcnmb1 in mice) subunit being predominantly expressed in smooth muscle. Thus, we hypothesize that BK β1 determines the effect of fentanyl on cerebral artery diameter. Here we report that fentanyl (0.001-10 μm) activates BK heteromers consisting of slo1 + β1 subunits in CHO cells, but not homomers of slo1. In ex vivo pressurized mouse cerebral arteries, pharmacological inhibition of BK or β1 genetic deletion (Kcnmb1-/-) led to fentanyl-induced vasoconstriction. Naloxone, an opioid receptor antagonist, ablates the fentanyl response in wild-type cerebral arteries whereas mild constriction persists in Kcnmb1-/- arteries. Therefore, we identify BK β1 as a functional fentanyl target which acts independently of opioid receptors to regulate fentanyl action on cerebral artery diameter.
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BibTeX
@article{thapa2026beta1,
title = {{Beta1 subunits enable fentanyl-induced BK channel activation and opioid regulation of cerebral artery diameter.}},
author = {Shiwani Thapa and Mohammed Nooh and Akhil Geddati and Alex Dopico and Anna N Bukiya},
journal = {FEBS open bio},
year = {2026},
month = oct,
doi = {10.1002/2211-5463.70347},
url = {https://europepmc.org/article/MED/42920409},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beta1 subunits enable fentanyl-induced BK channel activation and opioid regulation of cerebral artery diameter.
AU - Shiwani Thapa
AU - Mohammed Nooh
AU - Akhil Geddati
AU - Alex Dopico
AU - Anna N Bukiya
PY - 2026
DA - 2026/10/24
JO - FEBS open bio
DO - 10.1002/2211-5463.70347
UR - https://europepmc.org/article/MED/42920409
AB - Ultra-potent synthetic opioids are powerful analgesics but also a leading cause of drug overdose deaths. Calcium-/voltage-gated potassium channels of large conductance (BK) control vital physiological processes, with their accessory β1 (encoded by Kcnmb1 in mice) subunit being predominantly expressed in smooth muscle. Thus, we hypothesize that BK β1 determines the effect of fentanyl on cerebral artery diameter. Here we report that fentanyl (0.001-10 μm) activates BK heteromers consisting of slo1 + β1 subunits in CHO cells, but not homomers of slo1. In ex vivo pressurized mouse cerebral arteries, pharmacological inhibition of BK or β1 genetic deletion (Kcnmb1-/-) led to fentanyl-induced vasoconstriction. Naloxone, an opioid receptor antagonist, ablates the fentanyl response in wild-type cerebral arteries whereas mild constriction persists in Kcnmb1-/- arteries. Therefore, we identify BK β1 as a functional fentanyl target which acts independently of opioid receptors to regulate fentanyl action on cerebral artery diameter.
SN - 2211-5463
ER -