Denervation alters myosin heavy chain expression and contractility of developing rat diaphragm muscle

We hypothesized that unilateral denervation (DNV) of the rat diaphragm muscle (Dia_m) in neonates at postnatal day 7 (D-7) alters normal transitions of myosin heavy chain (MHC) isoform expression and thereby affects postnatal changes in maximum specific force (P_o) and maximum unloaded shortening velocity (V_o). The relative expression of different MHC isoforms was analyzed electrophoretically. With DNV at D-7, expression of MHC_neo in the Dia_m persisted, and emergence of MHC_2x and MHC_2B was delayed. By D-21 and D-28, relative expression of MHC_2A and MHC_2B was reduced in DNV compared with control (CTL) animals. Expression of MHC_neo also reappeared in adult Dia_m by 2-3 wk after DNV, and relative expression of MHC_2B was reduced. At each age, P_o was reduced and V_o was slowed by DNV, compared with CTL. In CTL Dia_m, postnatal changes in P_o and V_o were associated with an increase in fast MHC isoform expression. In DNV Dia_m, no such association existed. We conclude that, in the Dia_m, DNV induces alterations in both MHC isoform expression and contractile properties, which are not necessarily causally linked.