Beta-adrenergic potentiation of E-C coupling increases force in rat skeletal muscle.
We examined the mechanism(s) which allow terbutaline, a beta 2-adrenergic agonist, to increase isometric force in bundles of normal and denervated rat soleus fibers. Terbutaline (10 mumol/L) potentiated tetanic contractions during exposure to 1 mmol/L ouabain, 10 mumol/L nifedipine, or 0.5 mmol/L iodoacetate. Terbutaline induced equivalent increases in submaximal potassium (K+) contracture and tetanic force: these effects were mimicked by 2 mmol/L dibutyryl-cyclic AMP. Therefore, terbutaline increased force by a cyclic AMP-dependent mechanism other than enhancement of sodium-pump activity, dihydropyridine sensitive Ca2+ currents, glycolysis, or action potentials. Pretreatment with 1 mmol/L caffeine induced submaximal potentiation of peak tetanic force but prevented further potentiation by terbutaline. This suggested that terbutaline did not influence the myofilaments, but acted on the sarcoplasmic reticulum (SR) to increase the myoplasmic Ca2+ concentration and hence force production. We speculate that force is potentiated following beta-adrenoceptor activation by a cyclic AMP-dependent phosphorylation of Ca2+ release channels to facilitate SR calcium release during tetanic stimulation.
Cairns
S P
SP
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra.
Dulhunty
A F
AF
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D007461:Iodoacetates; D011943:Receptors, Adrenergic, beta; D010042:Ouabain; D003994:Bucladesine; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine; D011188:Potassium; D019807:Iodoacetic Acid