Modulation of the molecular composition of large conductance, Ca 2+ activated K+ channels in vascular smooth muscle during hypertension

Gregory C. Amberg, Adrian D. Bonev, Charles F. Rossow, Mark T. Nelson, Luis Fernando Santana

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

Hypertension is a clinical syndrome characterized by increased vascular tone. However, the molecular mechanisms underlying vascular dysfunction during acquired hypertension remain unresolved. Localized intracellular Ca 2+ release events through ryanodine receptors (Ca2+ sparks) in the sarcoplasmic reticulum are tightly coupled to the activation of large-conductance, Ca2+-activated K+ (BK) channels to provide a hyperpolarizing influence that opposes vasoconstriction. In this study we tested the hypothesis that a reduction in Ca2+ spark-BK channel coupling underlies vascular smooth muscle dysfunction during acquired hypertension. We found that in hypertension, expression of the β1 subunit was decreased relative to the pore-forming α subunit of the BK channel. Consequently, the BK channels were functionally uncoupled from Ca2+ sparks. Consistent with this, the contribution of BK channels to vascular tone was reduced during hypertension. We conclude that downregulation of the β1 subunit of the BK channel contributes to vascular dysfunction in hypertension. These results support the novel concept that changes in BK channel subunit composition regulate arterial smooth muscle function.

Original languageEnglish (US)
Pages (from-to)717-724
Number of pages8
JournalJournal of Clinical Investigation
Volume112
Issue number5
DOIs
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Vascular Smooth Muscle
Hypertension
Blood Vessels
Calcium-Activated Potassium Channels
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum
Vasoconstriction
Smooth Muscle
Down-Regulation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Modulation of the molecular composition of large conductance, Ca 2+ activated K+ channels in vascular smooth muscle during hypertension. / Amberg, Gregory C.; Bonev, Adrian D.; Rossow, Charles F.; Nelson, Mark T.; Santana, Luis Fernando.

In: Journal of Clinical Investigation, Vol. 112, No. 5, 09.2003, p. 717-724.

Research output: Contribution to journalArticle

@article{55b3bfe0f873467b8a310bdf9b419a8f,
title = "Modulation of the molecular composition of large conductance, Ca 2+ activated K+ channels in vascular smooth muscle during hypertension",
abstract = "Hypertension is a clinical syndrome characterized by increased vascular tone. However, the molecular mechanisms underlying vascular dysfunction during acquired hypertension remain unresolved. Localized intracellular Ca 2+ release events through ryanodine receptors (Ca2+ sparks) in the sarcoplasmic reticulum are tightly coupled to the activation of large-conductance, Ca2+-activated K+ (BK) channels to provide a hyperpolarizing influence that opposes vasoconstriction. In this study we tested the hypothesis that a reduction in Ca2+ spark-BK channel coupling underlies vascular smooth muscle dysfunction during acquired hypertension. We found that in hypertension, expression of the β1 subunit was decreased relative to the pore-forming α subunit of the BK channel. Consequently, the BK channels were functionally uncoupled from Ca2+ sparks. Consistent with this, the contribution of BK channels to vascular tone was reduced during hypertension. We conclude that downregulation of the β1 subunit of the BK channel contributes to vascular dysfunction in hypertension. These results support the novel concept that changes in BK channel subunit composition regulate arterial smooth muscle function.",
author = "Amberg, {Gregory C.} and Bonev, {Adrian D.} and Rossow, {Charles F.} and Nelson, {Mark T.} and Santana, {Luis Fernando}",
year = "2003",
month = "9",
doi = "10.1172/JCI200318684",
language = "English (US)",
volume = "112",
pages = "717--724",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

TY - JOUR

T1 - Modulation of the molecular composition of large conductance, Ca 2+ activated K+ channels in vascular smooth muscle during hypertension

AU - Amberg, Gregory C.

AU - Bonev, Adrian D.

AU - Rossow, Charles F.

AU - Nelson, Mark T.

AU - Santana, Luis Fernando

PY - 2003/9

Y1 - 2003/9

N2 - Hypertension is a clinical syndrome characterized by increased vascular tone. However, the molecular mechanisms underlying vascular dysfunction during acquired hypertension remain unresolved. Localized intracellular Ca 2+ release events through ryanodine receptors (Ca2+ sparks) in the sarcoplasmic reticulum are tightly coupled to the activation of large-conductance, Ca2+-activated K+ (BK) channels to provide a hyperpolarizing influence that opposes vasoconstriction. In this study we tested the hypothesis that a reduction in Ca2+ spark-BK channel coupling underlies vascular smooth muscle dysfunction during acquired hypertension. We found that in hypertension, expression of the β1 subunit was decreased relative to the pore-forming α subunit of the BK channel. Consequently, the BK channels were functionally uncoupled from Ca2+ sparks. Consistent with this, the contribution of BK channels to vascular tone was reduced during hypertension. We conclude that downregulation of the β1 subunit of the BK channel contributes to vascular dysfunction in hypertension. These results support the novel concept that changes in BK channel subunit composition regulate arterial smooth muscle function.

AB - Hypertension is a clinical syndrome characterized by increased vascular tone. However, the molecular mechanisms underlying vascular dysfunction during acquired hypertension remain unresolved. Localized intracellular Ca 2+ release events through ryanodine receptors (Ca2+ sparks) in the sarcoplasmic reticulum are tightly coupled to the activation of large-conductance, Ca2+-activated K+ (BK) channels to provide a hyperpolarizing influence that opposes vasoconstriction. In this study we tested the hypothesis that a reduction in Ca2+ spark-BK channel coupling underlies vascular smooth muscle dysfunction during acquired hypertension. We found that in hypertension, expression of the β1 subunit was decreased relative to the pore-forming α subunit of the BK channel. Consequently, the BK channels were functionally uncoupled from Ca2+ sparks. Consistent with this, the contribution of BK channels to vascular tone was reduced during hypertension. We conclude that downregulation of the β1 subunit of the BK channel contributes to vascular dysfunction in hypertension. These results support the novel concept that changes in BK channel subunit composition regulate arterial smooth muscle function.

UR - http://www.scopus.com/inward/record.url?scp=0141612004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141612004&partnerID=8YFLogxK

U2 - 10.1172/JCI200318684

DO - 10.1172/JCI200318684

M3 - Article

C2 - 12952920

AN - SCOPUS:0141612004

VL - 112

SP - 717

EP - 724

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

ER -