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Principally, this effect could contribute to the negative inotropic effect of CCh, but similar to IK,CCh, the inhibition of ICa required higher CCh concentrations than were needed to inhibit force production or reduce AP duration in the intact sinoatrial preparations.
Inhibition of either MYPT-1 phosphorylation or [Ca2+]i-mediated MLCK activation, or both will thus inhibit force generation.
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Our results suggest that nAg, but not Ag+ alone, inhibits force production by the myocardium, that Ag in any form disrupts normal pacing of cardiac contractions, and that these responses are likely not due to cytotoxicity.
Among the four phosphorylation sites on cTnT, Thr-203 appeared to be the most important for modulation of cTn function in that it inhibited force as well as its Ca2+ sensitivity [ 33].
These inhibiting forces require for their maintenance a relatively high level of sensory input of appropriate quality and frequency.
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CCh concentrations (3·10-8 M - 7·10-8 M) that significantly inhibit atrial force have practically no effect on HR.
The dogma of physiology teaching states that vagal post-ganglionic nerves modulate the heart through acetylcholine (ACh) acting on muscarinic receptors (mAChRs) to slow heart rate, increase atrioventricular conduction and inhibit atrial force, with little influence on ventricular performance.
The half-maximal activation of IK,CCh was attained at the concentration of ~3×10-7 M which is almost an order of magnitude higher than needed to inhibit the force of contraction in sinoatrial preparations (P > 0.05) (Table 2) or to shorten the duration of atrial AP.
A series of concentrations of unlabeled ligands could inhibit the forces established between radioligands and receptors, which could be used to measure the equilibrium dissociation constants.
Similarly, the drugs butanedione monoxime (BDM) [ 207, 210] benzyl-toluene sulfonamide (BTS) [ 202] and blebbistatin [ 197], that are believed to inhibit main force-generating transitions, have similar effects.
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