Downregulation of the BK Channel β1 Subunit in Genetic Hypertension

Gregory C. Amberg, Luis Fernando Santana

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca2+ release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca2+ sparks) activate large-conductance, Ca 2+-sensitive K+ (BK) channels. Ca2+ sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca 2+ sparks and BK channel function in Wistar-Kyoto (WKY) rats with borderline hypertension and in spontaneously hypertensive rats (SHR), a widely used genetic model of severe hypertension. We found that the amplitude of spontaneous BK currents in WKY and SHR cells were smaller than in normotensive cells even though Ca2+ sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca2+ than normotensive cells. Our data indicate that decreased expression of the BK channel β1 subunit underlies the lower Ca2+ sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the β1 subunit during genetic borderline and severe hypertension reduced BK channel activity by decreasing the sensitivity of these channels to physiological changes in Ca2+. These results support the view that changes in the molecular composition of BK channels may be a fundamental event contributing to the development of vascular dysfunction during hypertension.

Original languageEnglish (US)
Pages (from-to)965-971
Number of pages7
JournalCirculation Research
Volume93
Issue number10
DOIs
StatePublished - Nov 14 2003
Externally publishedYes

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Down-Regulation
Hypertension
Inbred SHR Rats
Ryanodine
Inbred WKY Rats
Genetic Models
Sarcoplasmic Reticulum
Vasoconstriction
Vascular Smooth Muscle
Muscle Cells
Smooth Muscle
Blood Vessels

Keywords

  • Ca sparks
  • Iberiotoxin
  • Ryanodine receptors
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Downregulation of the BK Channel β1 Subunit in Genetic Hypertension. / Amberg, Gregory C.; Santana, Luis Fernando.

In: Circulation Research, Vol. 93, No. 10, 14.11.2003, p. 965-971.

Research output: Contribution to journalArticle

@article{6a2fb83700dc4ecb80014264e8511158,
title = "Downregulation of the BK Channel β1 Subunit in Genetic Hypertension",
abstract = "The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca2+ release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca2+ sparks) activate large-conductance, Ca 2+-sensitive K+ (BK) channels. Ca2+ sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca 2+ sparks and BK channel function in Wistar-Kyoto (WKY) rats with borderline hypertension and in spontaneously hypertensive rats (SHR), a widely used genetic model of severe hypertension. We found that the amplitude of spontaneous BK currents in WKY and SHR cells were smaller than in normotensive cells even though Ca2+ sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca2+ than normotensive cells. Our data indicate that decreased expression of the BK channel β1 subunit underlies the lower Ca2+ sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the β1 subunit during genetic borderline and severe hypertension reduced BK channel activity by decreasing the sensitivity of these channels to physiological changes in Ca2+. These results support the view that changes in the molecular composition of BK channels may be a fundamental event contributing to the development of vascular dysfunction during hypertension.",
keywords = "Ca sparks, Iberiotoxin, Ryanodine receptors, Sarcoplasmic reticulum",
author = "Amberg, {Gregory C.} and Santana, {Luis Fernando}",
year = "2003",
month = "11",
day = "14",
doi = "10.1161/01.RES.0000100068.43006.36",
language = "English (US)",
volume = "93",
pages = "965--971",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Downregulation of the BK Channel β1 Subunit in Genetic Hypertension

AU - Amberg, Gregory C.

AU - Santana, Luis Fernando

PY - 2003/11/14

Y1 - 2003/11/14

N2 - The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca2+ release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca2+ sparks) activate large-conductance, Ca 2+-sensitive K+ (BK) channels. Ca2+ sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca 2+ sparks and BK channel function in Wistar-Kyoto (WKY) rats with borderline hypertension and in spontaneously hypertensive rats (SHR), a widely used genetic model of severe hypertension. We found that the amplitude of spontaneous BK currents in WKY and SHR cells were smaller than in normotensive cells even though Ca2+ sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca2+ than normotensive cells. Our data indicate that decreased expression of the BK channel β1 subunit underlies the lower Ca2+ sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the β1 subunit during genetic borderline and severe hypertension reduced BK channel activity by decreasing the sensitivity of these channels to physiological changes in Ca2+. These results support the view that changes in the molecular composition of BK channels may be a fundamental event contributing to the development of vascular dysfunction during hypertension.

AB - The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca2+ release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca2+ sparks) activate large-conductance, Ca 2+-sensitive K+ (BK) channels. Ca2+ sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca 2+ sparks and BK channel function in Wistar-Kyoto (WKY) rats with borderline hypertension and in spontaneously hypertensive rats (SHR), a widely used genetic model of severe hypertension. We found that the amplitude of spontaneous BK currents in WKY and SHR cells were smaller than in normotensive cells even though Ca2+ sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca2+ than normotensive cells. Our data indicate that decreased expression of the BK channel β1 subunit underlies the lower Ca2+ sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the β1 subunit during genetic borderline and severe hypertension reduced BK channel activity by decreasing the sensitivity of these channels to physiological changes in Ca2+. These results support the view that changes in the molecular composition of BK channels may be a fundamental event contributing to the development of vascular dysfunction during hypertension.

KW - Ca sparks

KW - Iberiotoxin

KW - Ryanodine receptors

KW - Sarcoplasmic reticulum

UR - http://www.scopus.com/inward/record.url?scp=0242460508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242460508&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000100068.43006.36

DO - 10.1161/01.RES.0000100068.43006.36

M3 - Article

VL - 93

SP - 965

EP - 971

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 10

ER -