Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy.
STREX alternative-exon adds to Slo channel a phosphorylation sequence that can invert protein kinase A (PKA) regulation from excitatory to inhibitory. Because pregnancy switches Slo responsiveness to PKA from inhibitory to excitatory, we hypothesized that STREX expression diminishes with pregnancy and is regulated by sex hormones. Different from total-rSlo, which is elevated around mid-pregnancy and decreases at term, STREX transcripts progressively decreased with pregnancy near 80% at term. STREX downregulation was mimicked by estrogen, and opposed by estrogen-receptor antagonist ICI 182,780 or progesterone (Pg). The regulation of STREX splicing directed by estrogen and Pg provides a mechanism for Slo's PKA-related phenotypic alteration with pregnancy.
Zhu
Ning
N
Department of Anesthesiology, Division of Molecular Medicine, University of California Los Angeles, Los Angeles, CA 90095-7115, USA.
Eghbali
Mansoureh
M
Helguera
Gustavo
G
Song
Min
M
Stefani
Enrico
E
Toro
Ligia
L
D017398:Alternative Splicing; D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D004965:Estrogen Antagonists / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005091:Exons; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010052:Ovariectomy; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D011487:Protein Conformation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004965:Estrogen Antagonists; D004967:Estrogens; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D020033:Protein Isoforms; D000077267:Fulvestrant; D011374:Progesterone; D004958:Estradiol