Smooth muscle cholesterol enables BK β1 subunit-mediated channel inhibition and subsequent vasoconstriction evoked by alcohol

Anna Bukiya, Thirumalini Vaithianathan, Guruprasad Kuntamallappanavar, Maria Asuncion-Chin, Alejandro Dopico

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objective-: Hypercholesterolemia and alcohol drinking constitute independent risk factors for cerebrovascular disease. Alcohol constricts cerebral arteries in several species, including humans. This action results from inhibition of voltage-and calcium-gated potassium channels (BK) in vascular smooth muscle cells (VSMC). BK activity is also modulated by membrane cholesterol. We investigated whether VSMC cholesterol regulates ethanol actions on BK and cerebral arteries. Methods and Results-: After myogenic tone development, cholesterol depletion of rat, resistance-size cerebral arteries ablated ethanol-induced constriction, a result that was identical in intact and endothelium-free vessels. Cholesterol depletion reduced ethanol inhibition of BK whether the channel was studied in VSMC or after rat cerebral artery myocyte subunit (cbv1+β1) reconstitution into phospholipid bilayers. Homomeric cbv1 channels reconstituted into bilayers and VSMC BK from β1 knockout mice were both resistant to ethanol-induced inhibition. Moreover, arteries from β1 knockout mice failed to respond to ethanol even when VSMC cholesterol was kept unmodified. Remarkably, ethanol inhibition of cbv1+β1 in bilayers and wt mouse VSMC BK were drastically blunted by cholesterol depletion. Consistently, cholesterol depletion suppressed ethanol constriction of wt mouse arteries. Conclusion-: VSMC cholesterol and BK β1 are both required for ethanol inhibition of BK and the resulting cerebral artery constriction, with health-related implications for manipulating cholesterol levels in alcohol-induced cerebrovascular disease.

Original languageEnglish (US)
Pages (from-to)2410-2423
Number of pages14
JournalArteriosclerosis, thrombosis, and vascular biology
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2011

Fingerprint

Vasoconstriction
Smooth Muscle
Vascular Smooth Muscle
Cholesterol
Alcohols
Ethanol
Smooth Muscle Myocytes
Cerebral Arteries
Constriction
Cerebrovascular Disorders
Knockout Mice
Arteries
Large-Conductance Calcium-Activated Potassium Channels
Voltage-Gated Potassium Channels
Inhibition (Psychology)
Hypercholesterolemia
Alcohol Drinking
Muscle Cells
Endothelium
Phospholipids

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Smooth muscle cholesterol enables BK β1 subunit-mediated channel inhibition and subsequent vasoconstriction evoked by alcohol. / Bukiya, Anna; Vaithianathan, Thirumalini; Kuntamallappanavar, Guruprasad; Asuncion-Chin, Maria; Dopico, Alejandro.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 31, No. 11, 01.11.2011, p. 2410-2423.

Research output: Contribution to journalArticle

@article{b3ae76f7d4a54d25bb955b5052190b5d,
title = "Smooth muscle cholesterol enables BK β1 subunit-mediated channel inhibition and subsequent vasoconstriction evoked by alcohol",
abstract = "Objective-: Hypercholesterolemia and alcohol drinking constitute independent risk factors for cerebrovascular disease. Alcohol constricts cerebral arteries in several species, including humans. This action results from inhibition of voltage-and calcium-gated potassium channels (BK) in vascular smooth muscle cells (VSMC). BK activity is also modulated by membrane cholesterol. We investigated whether VSMC cholesterol regulates ethanol actions on BK and cerebral arteries. Methods and Results-: After myogenic tone development, cholesterol depletion of rat, resistance-size cerebral arteries ablated ethanol-induced constriction, a result that was identical in intact and endothelium-free vessels. Cholesterol depletion reduced ethanol inhibition of BK whether the channel was studied in VSMC or after rat cerebral artery myocyte subunit (cbv1+β1) reconstitution into phospholipid bilayers. Homomeric cbv1 channels reconstituted into bilayers and VSMC BK from β1 knockout mice were both resistant to ethanol-induced inhibition. Moreover, arteries from β1 knockout mice failed to respond to ethanol even when VSMC cholesterol was kept unmodified. Remarkably, ethanol inhibition of cbv1+β1 in bilayers and wt mouse VSMC BK were drastically blunted by cholesterol depletion. Consistently, cholesterol depletion suppressed ethanol constriction of wt mouse arteries. Conclusion-: VSMC cholesterol and BK β1 are both required for ethanol inhibition of BK and the resulting cerebral artery constriction, with health-related implications for manipulating cholesterol levels in alcohol-induced cerebrovascular disease.",
author = "Anna Bukiya and Thirumalini Vaithianathan and Guruprasad Kuntamallappanavar and Maria Asuncion-Chin and Alejandro Dopico",
year = "2011",
month = "11",
day = "1",
doi = "10.1161/ATVBAHA.111.233965",
language = "English (US)",
volume = "31",
pages = "2410--2423",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Smooth muscle cholesterol enables BK β1 subunit-mediated channel inhibition and subsequent vasoconstriction evoked by alcohol

AU - Bukiya, Anna

AU - Vaithianathan, Thirumalini

AU - Kuntamallappanavar, Guruprasad

AU - Asuncion-Chin, Maria

AU - Dopico, Alejandro

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Objective-: Hypercholesterolemia and alcohol drinking constitute independent risk factors for cerebrovascular disease. Alcohol constricts cerebral arteries in several species, including humans. This action results from inhibition of voltage-and calcium-gated potassium channels (BK) in vascular smooth muscle cells (VSMC). BK activity is also modulated by membrane cholesterol. We investigated whether VSMC cholesterol regulates ethanol actions on BK and cerebral arteries. Methods and Results-: After myogenic tone development, cholesterol depletion of rat, resistance-size cerebral arteries ablated ethanol-induced constriction, a result that was identical in intact and endothelium-free vessels. Cholesterol depletion reduced ethanol inhibition of BK whether the channel was studied in VSMC or after rat cerebral artery myocyte subunit (cbv1+β1) reconstitution into phospholipid bilayers. Homomeric cbv1 channels reconstituted into bilayers and VSMC BK from β1 knockout mice were both resistant to ethanol-induced inhibition. Moreover, arteries from β1 knockout mice failed to respond to ethanol even when VSMC cholesterol was kept unmodified. Remarkably, ethanol inhibition of cbv1+β1 in bilayers and wt mouse VSMC BK were drastically blunted by cholesterol depletion. Consistently, cholesterol depletion suppressed ethanol constriction of wt mouse arteries. Conclusion-: VSMC cholesterol and BK β1 are both required for ethanol inhibition of BK and the resulting cerebral artery constriction, with health-related implications for manipulating cholesterol levels in alcohol-induced cerebrovascular disease.

AB - Objective-: Hypercholesterolemia and alcohol drinking constitute independent risk factors for cerebrovascular disease. Alcohol constricts cerebral arteries in several species, including humans. This action results from inhibition of voltage-and calcium-gated potassium channels (BK) in vascular smooth muscle cells (VSMC). BK activity is also modulated by membrane cholesterol. We investigated whether VSMC cholesterol regulates ethanol actions on BK and cerebral arteries. Methods and Results-: After myogenic tone development, cholesterol depletion of rat, resistance-size cerebral arteries ablated ethanol-induced constriction, a result that was identical in intact and endothelium-free vessels. Cholesterol depletion reduced ethanol inhibition of BK whether the channel was studied in VSMC or after rat cerebral artery myocyte subunit (cbv1+β1) reconstitution into phospholipid bilayers. Homomeric cbv1 channels reconstituted into bilayers and VSMC BK from β1 knockout mice were both resistant to ethanol-induced inhibition. Moreover, arteries from β1 knockout mice failed to respond to ethanol even when VSMC cholesterol was kept unmodified. Remarkably, ethanol inhibition of cbv1+β1 in bilayers and wt mouse VSMC BK were drastically blunted by cholesterol depletion. Consistently, cholesterol depletion suppressed ethanol constriction of wt mouse arteries. Conclusion-: VSMC cholesterol and BK β1 are both required for ethanol inhibition of BK and the resulting cerebral artery constriction, with health-related implications for manipulating cholesterol levels in alcohol-induced cerebrovascular disease.

UR - http://www.scopus.com/inward/record.url?scp=80054955816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054955816&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.111.233965

DO - 10.1161/ATVBAHA.111.233965

M3 - Article

VL - 31

SP - 2410

EP - 2423

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 11

ER -