RGD Reference Report - Differential regulation of transient receptor potential melastatin 6 and 7 cation channels by ANG II in vascular smooth muscle cells from spontaneously hypertensive rats. - Rat Genome Database

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Differential regulation of transient receptor potential melastatin 6 and 7 cation channels by ANG II in vascular smooth muscle cells from spontaneously hypertensive rats.

Authors: Touyz, RM  He, Y  Montezano, AC  Yao, G  Chubanov, V  Gudermann, T  Callera, GE 
Citation: Touyz RM, etal., Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R73-8. Epub 2005 Aug 18.
RGD ID: 1599668
Pubmed: PMID:16109804   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpregu.00515.2005   (Journal Full-text)

Intracellular Mg2+ depletion has been implicated in vascular dysfunction in hypertension. We demonstrated that transient receptor potential melastatin 7 (TRPM7) cation channels mediate Mg2+ influx in VSMCs. Whether this plays a role in [Mg2+]i deficiency in hypertension is unclear. Here, we tested the hypothesis that downregulation of TRPM7 and its homologue TRPM6 is associated with reduced [Mg2+]i and that ANG II negatively regulates TRPM6/7 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). Cultured VSMCs from Wistar Kyoto (WKY) and SHR were studied. mRNA and protein expression of TRPM6 and TRPM7 were assessed by RT-PCR and immunoblotting, respectively. Translocation of annexin-1, specific TRPM7 substrate, was measured as an index of TRPM7 activation. [Mg2+]i was determined using mag fura-2. VSMCs from WKY and SHR express TRPM6 and TRPM7. Basal TRPM6 expression was similar in WKY and SHR, but basal TRPM7 content was lower in VSMCs from SHR vs. WKY. This was associated with significantly reduced [Mg2+]i in SHR cells (P < 0.01). ANG II time-dependently increased TRPM6 expression, with similar responses in WKY and SHR. ANG II significantly increased TRPM7 expression in WKY (P < 0.05), but not in SHR. Annexin-1 translocation was reduced 1.5-2-fold in SHR vs. WKY. Our findings demonstrate that TRPM6 and TRPM7 are differentially regulated in VSMCs from SHR and WKY. Whereas TRPM6 is unaltered in SHR, expression of TRPM7 is blunted. This was associated with attenuated annexin-1 translocation and decreased VSMC [Mg2+]i in SHR. Downregulation of TRPM7, but not TRPM6, may play a role in altered Mg2+ homeostasis in VSMCs from SHR.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ANXA1Humanhypertension  ISOAnxa1 (Rattus norvegicus)protein:altered localization:vascular associated smooth muscle cellRGD 
Anxa1Rathypertension  IEP protein:altered localization:vascular associated smooth muscle cellRGD 
Anxa1Mousehypertension  ISOAnxa1 (Rattus norvegicus)protein:altered localization:vascular associated smooth muscle cellRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Trpm6Ratmonoatomic cation channel activity  NAS  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Anxa1  (annexin A1)
Trpm6  (transient receptor potential cation channel, subfamily M, member 6)

Genes (Mus musculus)
Anxa1  (annexin A1)

Genes (Homo sapiens)
ANXA1  (annexin A1)


Additional Information