Inhibitory effects of (±)‐propranolol on excitation‐contraction coupling in isolated soleus muscles of the rat

Abstract

1 The e ect of a b-adrenoceptor antagonist, propranolol, was investigated on excitation-contraction coupling in small, intact bundles of soleus muscle ®bres from the rat. 2 (+)-Propranolol signi®cantly inhibited twitch and tetanic tension with IC 50 values of 6.7 mM and 3.5 mM, respectively. 3 (+)-Propranolol (which has 100 times less b-blocking activity than the (+) form) was approximately one third as e ective as the (+) form at inhibiting isometric tension. 4 (+)-Propranolol (20 mM) had no signi®cant e ect on the amplitude of ca eine contractures, suggesting that it did not directly inhibit Ca 2+ release from the sarcoplasmic reticulum. 5 The resting membrane potential measured after 15 min perfusion with 20 mM (+)-propranolol was not signi®cantly di erent from control. However, this concentration of (+)-propranolol signi®cantly reduced both the peak amplitude and the maximum rate of rise of the action potential. Both e ects were only partially reversible after extensive washing. 6 (+)-Propranolol perfusion caused a modest reduction in the amplitude of sub-maximal K + contractures at concentrations (5 mM) that markedly depressed tetanic tension. 7 The results indicate that (+)-propranolol can decrease isometric tension independently of b-receptor occupation by (i) reducing the amplitude and rate of rise of the action potential and (ii) by directly inhibiting excitation-contraction coupling. The relatively low IC 50 for the`membrane-stabilizing' action of propranolol on tetanic tension (3.5 mM), combined with the ability of the drug to accumulate gradually in biological membranes, may contribute to a peripheral component of the tremorolytic and fatigue-inducing actions of propranolol on skeletal muscle.

Acute inhibitory effects of clenbuterol on force, Ca2+ transients and action potentials in rat soleus may not involve the β2‐adrenoceptor pathway

“…These results are the opposite of those obtained in previous studies with the classical β 2 ‐agonist, terbutaline, where terbutaline increased the Ca 2+ transient and twitch force. Both terbutaline responses were significantly inhibited by β 2 ‐adrenoceptor antagonists, suggesting that there was not a second pathway of action in the case of terbutaline 19,24–28 . The most logical inference to be drawn here is that a large component of clenbuterol’s actions occur via a pathway other than the surface β 2 ‐adrenoceptors.…”

cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

“…cyclic AMP; skeletal muscle; cell signaling; muscle regeneration; atrophy; protein kinase A ORIGINALLY DISCOVERED by Sutherland and Rall in liver homogenates in 1958 (218), adenosine 3=,5=-monophosphate (cyclic AMP, or cAMP) has since been intensively studied and is one of the best-characterized signaling molecules. In skeletal muscle, acute cAMP signaling has been implicated in regulation of glycogenolysis (213), contractility (32,83,84,88,138,234), sarcoplasmic calcium dynamics (58,147,184,204), and recovery from sustained contractile activity (44, 162). The net result of acute cAMP action on the order of minutes in skeletal muscle can generally be described as increased contractile force and rapid recovery of ion balance, especially during prolonged contractions.…”

KB-R7943 inhibits Na+-dependent Mg2+ efflux in rat ventricular myocytes

“…/K ? pump) [17], and 100 lM propranolol (an antiarrhythmic drug with b-adrenoceptor blockade and general membrane stabilizing actions) [18]. None of these drugs had a significant effect on the Na ?…”