Smooth-muscle contraction without smooth-muscle myosin.
Here we have used gene-targeting to eliminate expression of smooth-muscle myosin heavy chain. Elimination of this gene does not affect expression of non-muscle myosin heavy chain, and knockout individuals typically survive for three days. Prolonged activation, by KCl depolarisation, of intact bladder preparations from wild-type neonatal mice produces an initial transient state (phase 1) of high force generation and maximal shortening velocity, which is followed by a sustained state (phase 2) characterized by low force generation and maximal shortening velocity. Similar preparations from knockout neonatal mice do not undergo phase 1, but exhibit a normal phase 2. We propose that, in neonatal smooth muscle phase 1 is generated by recruitment of smooth-muscle myosin heavy chain, whereas phase 2 can be generated by activation of non-muscle myosin heavy chain. We conclude that phase 1 becomes indispensable for survival and normal growth soon after birth, particularly for functions such as homeostasis and circulation.
Morano
I
I
Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strabe 10, D-13092 Berlin, Germany.
Chai
G X
GX
Baltas
L G
LG
Lamounier-Zepter
V
V
Lutsch
G
G
Kott
M
M
Haase
H
H
Bader
M
M
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D002478:Cells, Cultured; D004374:Ductus Arteriosus, Patent / Q000503:physiopathology; D005260:Female; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D007422:Intestines / Q000002:abnormalities / Q000502:physiology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000002:abnormalities / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D018995:Myosin Heavy Chains / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012083:Renin / Q000097:blood; D001743:Urinary Bladder / Q000002:abnormalities / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D007527:Isoenzymes; D020033:Protein Isoforms; D012333:RNA, Messenger; D011189:Potassium Chloride; D012083:Renin; D018995:Myosin Heavy Chains