Cyclic AMP inhibits contractility of detergent treated glycerol extracted cardiac muscle

Abstract

Glycerinated myocardial fibres treated with a detergent (Lubrol WX) and suspended in ATP salt solution produce half maximum isometric tension at pCa 6.2 (at pH 6.7). After addition of cyclic AMP (1-100 microM), the pCa required for half maximum activation is 5.9. c-AMP in concentrations of 1-100 microM induces a dose dependent inhibition (up to 40% at pCa6), and this effect can be amplified by the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine) 10(-4) M. The effect is similar in presence and absence of sodium fluoride 10 mM. Since in detergent treated skinned fibres the cell membrane and the sarcoplasmic reticulum are extracted and since the Ca2+ ion concentration was kept constant and buffered, we propose that c-AMP does not act via the cell membrane or the sarcoplasmic reticulum, but via phosphorylation of troponin I. The latter is the only component which becomes phosphorylated in skinned fibres during c-AMP induced relaxation, an effect which is also responsible for the inhibition of actomyosin ATPase at constant Ca2+ ion concentration (cf. Ray and England 1976).

Cardiovascular effects of the novel Ca2+‐sensitiser EMD 57033 in pigs at rest and during treadmill exercise

“…Similar ®ndings have been reported for levosimendan in healthy humans (Sundberg et al, 1995). It is possible that exercise-induced increments in b-adrenergic activity, via cAMP-mediated phosphorylation of troponin-l, neutralizes the levosimendan or EMD 57033-mediated increases in Ca 2+ responsiveness of the myo®laments (Herzig et al, 1981). In the present study, EMD 57033 produced an increase in contractility at all levels of exercise in the presence of b-adrenoceptor blockade, which is consonant with the hypothesis that during exercise in the normal heart a pharmacologically-induced increase in myo®lament sensitivity to Ca 2+ can be o set by very high levels of b-adrenergic activity.…”

Modulation of Ca2+ transients and contractile properties by beta‐adrenoceptor stimulation in ferret ventricular muscles.

“…The decrease in Ca2+ sensitivity of contractile elements by isoprenaline is due to cyclic AMP-dependent phosphorylation of troponin I as reported previously (Ray & England, 1976;Solaro et al 1976;McClellan & Winegrad, 1978;Mope, McClellan & Winegrad, 1980;Herzig et al 1981;Yamamoto & Ohtuki, 1982;Kranias et al 1985). The decrease in Ca2+ sensitivity, estimated using the tetanic contraction, appeared at about 10-8 M at which significant change in TR50 was observed.…”

“…A decrease in the Hill coefficient by isoprenaline which is not reported in the sarcolemma-free preparations is due to a change in the intracellular ionic environment produced following an increase in cyclic AMP concentration (McClellan & Winegrad, 1978;Mope et al 1980;Herzig et al 1981). The decline of tonic tension in tetanus in the presence of isoprenaline might be also due to the change in the intracellular ionic environment (for example H+).…”

Hypercontractile Properties of Cardiac Muscle Fibers in a Knock-in Mouse Model of Cardiac Myosin-binding Protein-C

“…Papillary muscles or trabeculae from left ventricle were dissected, tied to thin glass rods, and skinned overnight in ice-cold relaxing solution (mM: imidazole, 20; pH 6.8; ATP, 7.5; MgCl 2 , 10; NaN 3 , 1; EGTA, 4; leupeptin, 0.1; BDM, 20; total ionic strength, 130) containing 0.25-0.5% Triton X-100 (26). A relatively low buffer pH used in skinned fiber mechanical studies was reported to be beneficial for the functional preservation of the regulatory system (27). After washes with fresh relaxing buffer, fiber bundles 150 -200 m thin and 3-4 mm long were mounted isometrically between a position-controlled rigid post and a force transducer (AME AE 801, Horten Electronics, Norway) with nitroacetate glue (26).…”