Gh. Rossmanith et al., MECHANISM OF ACTION OF ENDOTHELIN IN RAT CARDIAC-MUSCLE - CROSS-BRIDGE KINETICS AND MYOSIN LIGHT-CHAIN PHOSPHORYLATION, Journal of physiology, 505(1), 1997, pp. 217-227
1. The molecular mechanism of inotropic action of endothelin was inves
tigated in rat ventricular muscle by studying its effects on character
istics of isometric twitch, barium-induced steady contracture and the
level of incorporation of P-32(i) into myosin light chain 2. 2. Exposu
re of rat papillary muscle to endothelin caused an increase in isometr
ic twitch force but did not alter the twitch-time parameters. 3. Endot
helin did not significantly change the maximum contracture tension but
did cause an increase in contracture tension at submaximal levels of
activation, without changes in the tension-to-stiffness ratio and kine
tics of attached cross-bridges. Kinetics of attached crossbridges were
deduced during steady contracture from complex-stiffness values, and
in particular from the frequency at which muscle stiffness assumes a m
inimum value, f(min). Endothelin did not alter f(min). 4. Endothelin c
aused an increase in the level of incorporation of P-32(i) into myosin
light chain 2 without a concurrent change in the level of incorporati
on of P-32(i) into troyonin I. 5. We conclude that the inotropic actio
n of endothelin is not due to an increase in the kinetics of attached
cross-bridges, nor due to a change in the force per unit cross-bridge,
but may result from an increased divalent cation sensitivity caused b
y elevated myosin light chain 2 phosphorylation, resembling post-tetan
ic potentiation in fast skeletal muscle fibres.