Smooth-muscle contraction without smooth-muscle myosin

Here we have used gene-targeting to eliminate expression of smooth-muscle m yosin heavy chain. Elimination of this gene does not affect expression of n on-muscle myosin heavy chain, and knockout individuals typically survive fo r three days. Prolonged activation, by KCI depolarisation, of intact bladde r preparations from wild-type neonatal mice produces an initial transient s tate (phase 1) of high force generation and maximal shortening velocity, wh ich is followed by a sustained state (phase 2) characterized by low force g eneration and maximal shortening velocity. Similar preparations from knocko ut neonatal mice do not undergo phase 1, but exhibit a normal phase 2. We p ropose that, in neonatal smooth muscle phase 1 is generated by recruitment of smooth-muscle myosin heavy chain, whereas phase 2 can be generated by ac tivation of non-muscle myosin heavy chain. We conclude that phase 1 becomes indispensable for survival and normal growth soon after birth, particularl y for functions such as homeostasis and circulation.