RGD Reference Report - Downregulation of the BK channel beta1 subunit in genetic hypertension. - Rat Genome Database

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Downregulation of the BK channel beta1 subunit in genetic hypertension.

Authors: Amberg, GC  Santana, LF 
Citation: Amberg GC and Santana LF, Circ Res 2003 Nov 14;93(10):965-71. Epub 2003 Oct 9.
RGD ID: 1298970
Pubmed: PMID:14551242   (View Abstract at PubMed)
DOI: DOI:10.1161/01.RES.0000100068.43006.36   (Journal Full-text)

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, Ca2+-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 Ca2+ 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 beta1 subunit underlies the lower Ca2+ sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the beta1 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOKcnmb1 (Rattus norvegicus)1298970; 1298970 RGD 
hypertension  IDA 1298970 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased systemic arterial blood pressure  IDA 1298970 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Kcnmb1  (potassium calcium-activated channel subfamily M regulatory beta subunit 1)

Genes (Mus musculus)
Kcnmb1  (potassium large conductance calcium-activated channel, subfamily M, beta member 1)

Genes (Homo sapiens)
KCNMB1  (potassium calcium-activated channel subfamily M regulatory beta subunit 1)


Additional Information