EXOGENOUS CALDESMON PROMOTES RELAXATION OF GUINEA-PIG SKINNED TAENIA-COLI SMOOTH MUSCLES - INHIBITION OF COOPERATIVE REATTACHMENT OF LATCH BRIDGES

In smooth muscle, the state of prolonged contraction (latch state) is associated with very slow energy turnover and cycling of crossbridges that are dephosphorylated. A similar state may be reproduced in skinne d fibres when the calcium-induced contraction is terminated by calcium removal with ethylenebis (oxonitrilo) tetraacetate (EGTA) and, during the slow relaxation that follows, force is maintained by dephosphoryl ated crossbridges that cycle slowly or not at all and may cooperativel y reattach after detachment (Khromov et al. 1995, Biophys J 69:2611-26 22). In guinea-pig skinned taenia coli that has been pretreated by pro longed incubation with caldesmon (5 mu M), the rate of relaxation is a pproximately 1.6 times greater than in untreated controls, with half-t imes of relaxation being 1.3 and 2.1 min, respectively. In contrast, p reloading the fibres with calponin does not accelerate relaxation. Pre loading the fibres with caldesmon also accelerates the relaxation of s kinned fibres from the state of rigor contraction when the latter is t erminated by immersion into an ATP-containing relaxing solution or, in the presence of inorganic phosphate (Pi), also by flash-photolytic re lease of ATP from caged-ATP. Even in the latter case, relaxation is co mparatively slow, possibly because of cooperative reattachment of deph osphorylated crossbridges which delays net crossbridge detachment and hence relaxation. We propose that by inhibition of cooperative reattac hment caldesmon accelerates relaxation, even in the presence of Pi, an d that the latch-like state of skinned fibres is supported by dephosph orylated cooperatively attaching crossbridges and may be regulated by the activity of caldesmon in the smooth muscle cell.