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Latrunculin B increases force fluctuation-induced relengthening of ACh-contracted, isotonically shortened canine tracheal smooth muscle.

We hypothesized that differences in actin filament length could influence force fluctuation-induced relengthening (FFIR) of contracted airway smooth muscle and tested this hypothesis as follows. One-hundred micromolar ACh-stimulated canine tracheal smooth muscle (TSM) strips set at optimal reference length (Lref) were allowed to shorten against 32% maximal isometric force (Fmax) steady preload, after which force oscillations of +/-16% Fmax were superimposed. Strips relengthened during force oscillations. We measured hysteresivity and calculated FFIR as the difference between muscle length before and after 20-min imposed force oscillations. Strips were relaxed by ACh removal and treated for 1 h with 30 nM latrunculin B (sequesters G-actin and promotes depolymerization) or 500 nM jasplakinolide (stabilizes actin filaments and opposes depolymerization). A second isotonic contraction protocol was then performed; FFIR and hysteresivity were again measured. Latrunculin B increased FFIR by 92.2 +/- 27.6% Lref and hysteresivity by 31.8 +/- 13.5% vs. pretreatment values. In contrast, jasplakinolide had little influence on relengthening by itself; neither FFIR nor hysteresivity was significantly affected. However, when jasplakinolide-treated tissues were then incubated with latrunculin B in the continued presence of jasplakinolide for 1 more h and a third contraction protocol performed, latrunculin B no longer substantially enhanced TSM relengthening. In TSM treated with latrunculin B + jasplakinolide, FFIR increased by only 3.03 +/- 5.2% Lref and hysteresivity by 4.14 +/- 4.9% compared with its first (pre-jasplakinolide or latrunculin B) value. These results suggest that actin filament length, in part, determines the relengthening of contracted airway smooth muscle.

Acetylcholine↗

Tendon organ sensitivity to steady-state isotonic contraction of in-series motor units in feline peroneus tertius muscle.

1. Measurements have been made of the sensitivity of tendon organs to steady-state, isotonic contractions of single and groups of in-series motor units in the peroneus tertius muscle of the cat hindlimb. 2. Linear relationships were found between the Ib afferent discharge and the contractile tension generated by tetanic stimulation of single motor units. These relationships held for the fast, fatiguable (FF) units and for all but the lowest tensions generated by the slow (S) and some fast, fatigue resistant (FR) units. The sensitivity of the organs was independent of the contractile properties of the units. 3. Groups of three motor units were stimulated isotonically at low rates (around 30 Hz), but asynchronously to produce a smooth tension profile. Again, linear relationships pertained between the discharge rate and the tension, and the sensitivity was the same for different motor unit types. 4. Under isotonic conditions, therefore, the tendon organs showed linear responses to the tension with similar sensitivities, indicating that tendon organs may have the capacity to signal faithfully steady-state contractile tensions.

Afferent Pathways↗

Agonist-induced isotonic contraction of cultured mesangial cells after multiple passage.

Contractile cells under conditions of prolonged culture lose their ability to contract in the usual manner (i.e., isotonically). One explanation for this may be that contraction is prevented by tight cell-to-substrate adhesion. Two models in which substrate adhesiveness was expected to be diminished were used to test this hypothesis. In one, cells were seeded onto collagen-coated dishes and used within 40 min of plating. In the other, cells were plated onto dishes coated with poly-2-hydroxyethyl methacrylate (poly-HEMA) and used, depending on thickness of the poly-HEMA substrate, up to periods of 1 wk. Cells plated onto such substrates contracted when challenged with either PGE2 (2 X 10(-6) and 2 X 10(-9) M), arginine vasopressin (AVP, 10(-6)-10(-9) ), or the calcium ionophore A23187 (5 micrograms/ml). Contraction took place within 5-15 min at 37 degrees C. The contraction seen with AVP was due to its pressor action because 1-desamino-8-D-arginine vasopressin (dDAVP), the antidiuretic analogue, did not cause contraction and the anti-pressor analogue [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid)-4-valine 8-D-arginine]-vasopressin [d(CH2)5-VDAVP] blocked contraction by AVP. The contraction seen with AVP was dependent on extracellular calcium, whereas that observed with prostaglandin E2 (PGE2) was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modulation of cutaneous cortical evoked potentials during isometric and isotonic contractions in the monkey.

The effects of the direction of movement (flexion vs extension) and the nature of the motor task (isotonic vs isometric) on the modulation of sensory cortical evoked responses to cutaneous stimulation were investigated in one monkey. Sensory responses were assessed by measuring the magnitude of the short latency component of air puff-evoked potentials recorded intracortically in the arm representation of areas 3b and 1 in the primary somatosensory cortex. At most recording sites, it was found that the amplitude of the air puff-evoked potential was decreased in a non-specific manner by motor activity. Neither the timing nor the depth of the modulation were found to vary with either the direction or the type of contraction. The effects were widespread since inputs from practically the entire forelimb (hairy skin) were diminished during the motor tasks. These results thus show that the modulation was more closely linked to the central motor output than to the peripheral input generated by muscle force and/or limb displacement. It is suggested that signals originating from central motor structures, acting in a feedforward manner, play a major role in 'gating' cutaneous inputs during movement. It is further suggested that the centrally mediated effects are exerted via a final common pathway upon which the 'gating' signals converge.

Animals↗

Isometric and isotonic contractions in airway smooth muscle.

Canine tracheal smooth muscle was used as an in vitro model of smooth muscle in intrapulmonary airways to determine whether active tension curves derived from isometric and isotonic muscles are similar, and thus resemble striated muscle in this respect. Isometric, isotonic after-loaded, and isotonic free-loaded contractions elicited at different lengths and loads, were analysed. The data demonstrate that length-tension (L-T) diagrams were different in these various types of contractions for electrically and carbachol driven tracheal smooth muscles strips. In general, at any given length active tension is less in isotonic and free-loaded modes of contraction as compared with isometric. We conclude that the ability to actively develop tension at a given length in airway smooth muscle depends on the mode of contraction.

Animals↗