Abstract 406: SM-2 Myosin Isoform is an Important Determinant of Contractile Properties in Tonic Versus Phasic Smooth Muscle
Mammalian smooth muscle is classified into tonic and phasic smooth muscle types. These muscles show different contractile properties but the cellular determinants underlying tonic and phasic smooth muscle contractile properties are still unclear. SM1 and SM2 myosin isoforms (differ in C-terminus) are expressed differently in tonic and phasic smooth muscle. SM2 is more prevalent in phasic muscle (e.g. bladder) compared to tonic muscle (e.g. aorta) and appears earlier in muscle development. To investigate if the ratio of SM1 and SM2 determine muscle contractile properties, we have recently generated a mouse model that is deficient in SM2 myosin but expresses SM1. SM2 null mice showed retarded growth, distention of bladder and alimentary tract, and severe hydronephrosis by 2 weeks after birth. Aorta from null mouse was structurally intact. Biochemical analysis showed that SM2 protein was completely absent in the SM2 null mice, and SM1 myosin levels were down regulated in the bladder. On the other hand, total myosin protein level was preserved in aorta. Functional analysis of SM2 null bladder showed an increase in sustained phase of force development and the muscle responded with an increased sensitivity to KCl at all doses. These data suggest that loss of SM2 converts the bladder to resemble a tonic phenotype. Interestingly, in SM2 null aorta isolated from day 1, there was no significant difference in isometric force generation and relaxation; whereas aorta from day 5 showed delayed relaxation. These data suggest that loss of SM2 myosin in phasic smooth muscle results in a tonic contractile state and loss of SM2 containing filaments in tonic smooth muscle leads to persistent tonic contraction as found in adult aorta. Therefore we conclude that SM2 myosin isoform is a major determinant of contractile property in phasic versus tonic smooth muscle.