Smooth muscle myosin heavy chains are developmentally regulated in the rabbit bladder

Purpose: In smooth muscle (SM), myosin heavy chain (MHC) is expressed predo minantly as two isoforms, SM1 and SM2, which are encoded by a single gene a nd expressed by alternative splicing mechanisms. Although functional differ ences of these isoforms are unknown, changes in SM1/SM2 ratio have been rep orted in various pathophysiologic conditions. We analyzed MHC composition o f bladder detrusor SM from rabbits of different ages to determine whether S M1 and SM2 isoform expressions are developmentally regulated. Materials and Methods: Rabbit bladders on the -11, -4, 1, 7, 14, 21, and 90 (th) days of life were analyzed for SM MHC isoform expression at protein an d mRNA levels. Porous sodium dodecyl sulfate polyacrylamide gel electrophor esis (SDS-PAGE), S1 protection assay, and histological analysis were employ ed. Results: The predominant MHC isoform in fetal and neonatal bladders was SM1 . In the third postnatal week, the SM1/SM2 ratio decreased from 2.3 to 1.0. A stable SM1/SM2 ratio of 0.6 was observed in the adult animal. Although e xpression of SM1 mRNA was 2.6-fold greater than that of SM2 in the fetus, t he relative amount of SM2 mRNA increased rapidly after birth and remained t he predominant isoform throughout adult life. Developmental changes in rela tive amounts of SM1 and SM2 protein in bladder tissues were virtually ident ical to those of SM1 and SM2 mRNA. SM cell growth and disappearance of prim itive mesenchyme from the bladder occurred concomitantly with the MHC isofo rm shift. Conclusions: The parallel temporal course of MHC mRNA and protein isoform l evels suggests detrusor SM MHC expression may be developmentally regulated at the mRNA level.