ACTIVATION OF PROTEIN-KINASE-C ACCELERATES CONTRACTION KINETICS OF AIRWAY SMOOTH-MUSCLE

Contraction kinetics of isolated rat tracheal smooth muscle were studi ed by analysing the increase of force subsequent to force-inhibiting p assive length changes lasting 1 s (100 Hz, sinus, 5% of muscle length) . Compared with carbachol activation, phorboldibutyrate (PDBu)-induced stimulation of protein kinase C (PKC) demonstrated no significant dif ference in the extent of force development in the polarized preparatio n [mean peak force 9.16 +/- 0.37 mN (carbachol) vs. 9.12 +/- 0.37 mN ( PDBu)]. However, the time constant calculated for the slow component o f postvibration force recovery was 6.40 +/- 0.29 s after addition of P DBu vs. 22.39 +/- 1.40 s during carbachol activation: indicating a sig nificant phorbol ester-induced acceleration of the cross-bridge cyclin g rate. In the K-depolarized preparation, treatment with 26.4 mu M ind olactam (IL) to activate PKC produced muscle relaxation (9.94 +/- 0.16 mN measured 0-30 min after the onset of depolarization vs. 4.13 +/- 0 .05 mN measured during 30-60 min of IL treatment). Again, even in the presence of high sarcoplasmic Ca resulting from tonic depolarization, PKC activation was associated with a distinct diminution of the time c onstant (25.99 +/- 0.79 s during the first 30 min of depolarization vs . 10.32 +/- 0.21 a during 30-60 min of IL treatment). In contrast, add ition of 0.035 mu M verapamil, 1.5 mu M isoproterenol, and 32 mu M dib utyryl-cAMP to the bathing medium induced relaxation without affecting the rate of post-vibration force recovery. The results suggest that t he calcium-dependent signal cascade (agonist receptor/inositol trispho sphate/Ca2+. calmodulin/myosin light chain kinase) hardly affects the regulation of contraction kinetics in the tonically activated intact s mooth muscle preparation. PKC stimulation, however, accelerates actin/ myosin interaction kinetics, possibly by inhibition of phosphatase(s).