Curare‐like Effect of Propranolol on Rat Extraocular Muscles

Abstract

1 The effects were studied of the ,B-adrenoceptor blocking drug, (±)propranolol and its (+) and (-)isomers on contractility of rat isolated diaphragm and inferior rectus muscles.2 Propranolol (10'-M) did not modify the resting tension nor the electrically-induced twitch contraction in diaphragm and extraocular muscles, nor the tonic tension evoked in the latter by high K concentrations.3 In inferior rectus preparations (± )-propranolol (5 x 10-6 M) reduced significantly tensions evoked by succinylcholine (SCh). Cumulative dose-response curves to SCh were shifted to the right in a nearly parallel manner by (+ )-and (--propranolol which were about equiactive. 4 It is concluded that the depressant action of propranolol is independent of its adrenoceptor blocking potency and it is not due to an alteration of the contraction mechanism. Propranolol appears to depress SCh-evoked tensions through a curare-like effect on cholinoceptors.

Measurement of contractile force of skeletal and extraocular muscles: Effects of blood supply, muscle size and in situ or in vitro preparation

“…Yet, these methods are advantageous because the muscle's origin is preserved, its orientation is largely conserved, and an intact blood supply maintains the viability of the muscle (Bach-yRita and Ito, 1966;Barmack et al, 1971;Hanson and Lennerstrand, 1977;Shall and Goldberg, 1992;Dimitrova et al, 2002;Shall et al, 2003). The relative ease of in vitro preparations for the determination of extraocular muscle force is reflected by their extensive use (Close and Luff, 1974;Luff, 1981;Chiarandini, 1980Chiarandini, , 1987Asmussen and Gaunitz, 1981;Jacoby et al, 1989;Chen and von Bartheld, 2004;McLoon et al, 2006;Anderson et al, 2006). While in vitro methods have the advantage of being technically less demanding and do not require general anesthesia, they may not be optimal for obtaining accurate contractile measurements of extraocular muscle.…”

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

“…A further indication of a membrane stabilizing action of (±)‐propranolol was shown by its ability to decrease markedly both the overshoot and the rate of rise of the intracellularly recorded action potential in the presence of (+)‐tubocurarine (Figure 6). This effect suggests a blocking action on voltage‐dependent sodium channels located in the sarcolemma and/or transverse tubular system, rather than a ‘curare‐like’ action of propranolol that has been previously suggested in mammalian skeletal muscle (Larsen & Teräväinen, 1978; Chiarandini, 1980). The effects of 20 μm (±)‐propranolol on action potentials in the present study (80% decrease in rate of rise, 50% decrease in amplitude) are quantitatively similar to those previously observed in rat diaphragm muscles at concentrations around 100 μm (Larsen, 1978), indicating a higher sensitivity of the rat soleus muscle to the effects of (±)‐propranolol.…”

“…These are the first experiments to characterize fully the complete concentration‐response relationship for the effects of (±)‐propranolol on skeletal muscle, yielding IC 50 values of ∼3.5 μm and ∼7 μm for the tetanus and twitch, respectively. Such values are low compared with the 25% inhibition of twitch tension seen with 50 μm (±)‐propranolol in rat inferior rectus muscles (Chiarandini, 1980) and are in complete contrast to the potentiation of twitch tension by 10 μm (±)‐propranolol seen in single frog skeletal muscle fibres (Oota & Nagai, 1977).…”

“…At therapeutic plasma concentrations (0.1 to 3 μm; Benet et al , 1996) propranolol acts primarily by blocking β‐adrenoceptors in the central nervous system and the periphery. However, receptor‐independent actions of the drug may occur in both cardiac (Morales‐Aguilerá & Vaughan‐Williams, 1965) and skeletal muscles (Oota & Nagai, 1977; Chiarandini, 1980) at higher concentrations.…”

“…At high concentrations (10 to 1000 μm) it has been suggested that propranolol directly inhibits skeletal muscle contraction by affecting the nicotinic cholinoceptors (Chiarandini, 1980), the action potential and excitation‐contraction coupling steps (Oota & Nagai, 1977), the sarcoplasmic reticulum (SR) Ca 2+ uptake pump (Noack et al , 1978; Su & Malencik, 1985), and the ryanodine receptor/SR Ca 2+ release channel (Zchut et al , 1996). It has been difficult to assess the exact contribution of any one site of action to the depression of contraction seen in intact skeletal muscles, because these studies have used widely varying types of muscle, differing degrees of muscle integrity and different propranolol concentration ranges.…”