TY - JOUR
T1 - Effect of 17β-estradiol on mRNA expression of large-conductance, voltage-dependent, and calcium-activated potassium channel α and β subunits in guinea pig
AU - Jamali, Khalid
AU - Naylor, Barry R.
AU - Kelly, Martin J.
AU - Rønnekleiv, Oline K.
N1 - Funding Information:
We thank Martha Bosch for excellent technical assistance. We are also grateful to Drs. Jeffrey Martens, Terry Wadsworth, and Charles Roselli for help with the Western blot analyses. This work was supported by NIH grant NS-35944, and Office of Research on Women’s Health, grants NS-38809 and DA05158.
PY - 2003/4
Y1 - 2003/4
N2 - Large-conductance, voltage- and calcium-activated potassium (MaxiK) channels play a key role in cell excitability. MaxiK channels are composed of a pore-forming α-subunit and a regulatory β-subunit, of which four (β1-4) genes have been identified. Previous findings suggested that MaxiK channel activity is regulated by estradiol. However, the underlying mechanisms have remained incompletely documented. Therefore, we used reverse transcriptase polymerase chain reaction to clone four cDNA fragments that were specific to the guinea pig α, β1, β2, and β4 genes. Using a sensitive ribonuclease protection assay, we found that the α and β4 mRNAs were the most abundant mRNAs in the brain and pituitary, whereas in the aorta, the α-subunit was coexpressed with the β1-subunit. Moreover, there was a significant upregulation of the α- but not the β1-subunit mRNA and the α-subunit protein in the aorta of the estrogenvs oil-treated ovariectomized animals. In specific brain areas including preoptic area, ventral hypothalamus, hippocampus, and amygdala, and in the pituitary, neither the α- nor β4-subunit mRNAs were affected by estrogen. These findings suggest that estrogen may not affect the mRNA expression of MaxiK channels in the brain and pituitary. However, estrogen causes increased expression of MaxiK α in the aorta, which may explain some of the cardioprotective effects of estrogen in women.
AB - Large-conductance, voltage- and calcium-activated potassium (MaxiK) channels play a key role in cell excitability. MaxiK channels are composed of a pore-forming α-subunit and a regulatory β-subunit, of which four (β1-4) genes have been identified. Previous findings suggested that MaxiK channel activity is regulated by estradiol. However, the underlying mechanisms have remained incompletely documented. Therefore, we used reverse transcriptase polymerase chain reaction to clone four cDNA fragments that were specific to the guinea pig α, β1, β2, and β4 genes. Using a sensitive ribonuclease protection assay, we found that the α and β4 mRNAs were the most abundant mRNAs in the brain and pituitary, whereas in the aorta, the α-subunit was coexpressed with the β1-subunit. Moreover, there was a significant upregulation of the α- but not the β1-subunit mRNA and the α-subunit protein in the aorta of the estrogenvs oil-treated ovariectomized animals. In specific brain areas including preoptic area, ventral hypothalamus, hippocampus, and amygdala, and in the pituitary, neither the α- nor β4-subunit mRNAs were affected by estrogen. These findings suggest that estrogen may not affect the mRNA expression of MaxiK channels in the brain and pituitary. However, estrogen causes increased expression of MaxiK α in the aorta, which may explain some of the cardioprotective effects of estrogen in women.
KW - Aorta
KW - Brain
KW - Estradiol effects
KW - MaxiK channel subunits
KW - mRNA expression
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U2 - 10.1385/ENDO:20:3:227
DO - 10.1385/ENDO:20:3:227
M3 - Article
C2 - 12721501
AN - SCOPUS:0038064494
SN - 1355-008X
VL - 20
SP - 227
EP - 237
JO - Endocrine
JF - Endocrine
IS - 3
ER -