Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3.
In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea or sudden infant death syndrome and for regulating uterine contractions during labor.
Bond
C T
CT
Vollum Institute, Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, OR 97201, USA.
Sprengel
R
R
Bissonnette
J M
JM
Kaufmann
W A
WA
Pribnow
D
D
Neelands
T
T
Storck
T
T
Baetscher
M
M
Jerecic
J
J
Maylie
J
J
Knaus
H G
HG
Seeburg
P H
PH
Adelman
J P
JP
D020121:5' Untranslated Regions; D000200:Action Potentials; D000818:Animals; D001921:Brain / Q000378:metabolism; D003433:Crosses, Genetic; D046508:Culture Techniques; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D018390:Gene Targeting; D000860:Hypoxia / Q000378:metabolism; D007743:Labor, Obstetric / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D011247:Pregnancy; D012143:Respiratory Physiological Phenomena; D051640:Small-Conductance Calcium-Activated Potassium Channels
D020121:5' Untranslated Regions; C496900:Kcnn3 protein, mouse; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D004318:Doxycycline