Substrate and product dependence of force and shortening in fast and slow smooth muscle

To explore the molecular mechanisms responsible for the variation in smooth muscle contractile kinetics, the influence of MgATP, MgADP, and inorganic phosphate (P-i) on force and shortening velocity in thiophosphorylated "fas t" (taenia coli: maximal shortening velocity V-max = 0.11 ML/s) and "slow" (aorta: V-max = 0.015 ML/s) smooth muscle from the guinea pig were compared . P-i inhibited active force with minor effects on the V-max. In the taenia coli, 20 mM P-i inhibited force by 25%. In the aorta, the effect was marke dly less (<10%), suggesting differences between fast and slow smooth muscle s in the binding of P-i or in the relative population of P-i binding states during cycling. Lowering of MgATP reduced force and V-max. The aorta was l ess sensitive to reduction in MgATP (K-m for V-max: 80 <mu>M) than the taen ia coli (K-m for V-max: 350 muM). Thus, velocity is controlled by steps pre ceding the ATP binding and cross-bridge dissociation, and a weaker binding of ATP is not responsible for the lower V-max in the slow muscle. MgADP inh ibited force and V-max. Saturating concentrations of ADP did not completely inhibit maximal shortening velocity. The effect of ADP on V-max was observ ed at lower concentrations in the aorta compared with the taenia coli, sugg esting that the ADP binding to phosphorylated and cycling cross-bridges is stonger in slow compared with fast smooth muscle.