SUMMARY1. Cable parameters, component conductances, excitability and membrane potentials in isolated external intercostal fibre bundles at 380 C from normal and myotonic goats were measured in normal and low-chloride Ringer, and in the presence of monocarboxylic aromatic acids that produce myotonic responses in mammalian muscle.2. The mean resting chloride conductance in gzmho/cm2 of myotonic fibres (range 0-147) was significantly less than that of normal fibres (range 376-951). The mean resting potassium conductance was higher in myotonic fibres (range 123-285) than in normal fibres (range 44-132).Potassium conductance increased about 10 ,smho/cm2 per mV increase in absolute resting potential.3. In normal fibres in normal Ringer 3-chloro-2,5,6-trimethylbenzoic acid; 5,6-dihydro-5,5-dimethyl-7-carboxybenz[c]acridine; phenanthrene-9-carboxylic acid; and anthracene-9-carboxylic acid at 10-5-104 M decreased membrane conductance without consistently changing diameter or capacitance. In low-chloride Ringer 3-chloro-2,5,6-trimethylbenzoic acid (5 x 10-5 M) increased potassium conductance in myotonic and normal fibres. It is concluded that these compounds block chloride conductance.4. The carboxylic acids produced myotonia in normal fibres similar to that in untreated myotonic fibres.5. Anthracene-9-carboxylic acid intravenously (8 mg/kg) in normal goats produced acutely a condition resembling myotonia congenita. The carboxylic acids produced no myotonic effects in frog muscle.

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The aim of this experimental study was to analyze in vitro effects of clofibric acid on vimentin and desmin contents in rat myocardiocytes, which was carried out in primary myocardiocyte cells that were treated only with clofibric acid at 0.1 mM. The measurement of vimentin and desmin were done by Western blotting and densitometry. This study showed that myocardiocytes exposed to clofibric acid exhibit a 26.3% decrease in vimentin and a 42.1% decrease in desmin. Considering the role that these intermediate filaments play in the anchorage and cellular organization of myocardiocytes, the decrease of desmin and vimentin observed in cells treated with clofibric acid may be partially responsible for the adverse effects observed in patients. In conclusion, the alteration of cytoskeletal proteins may be a cause of cardiopathy in patients treated with these compounds.

Pronethalol was shown by Black & Stephenson (1962) to have many actions consistent with the view that its chief effect was blockade of sympathetic P-receptors. For example, in cats anaesthetized with chloralose, 2.5 mg/kg of pronethalol halved, and 5 mg/kg reduced by nine-tenths, submaximal accelerations of heart rate produced by injections of isoprenaline. However, in guinea-pigs anaesthetized with urethane (1.6 g/kg), it was found (Sekiya & Vaughan Williams, 1963a) that, although pronethalol (10 mg/kg) approximately halved the spontaneous heart rate, responses to isoprenaline were reduced to a lesser extent. Actions of pronethalol other than fl-receptor blockade also came to light, and it was shown (Gill & Vaughan Williams, 1964) that pronethalol was a local anaesthetic with nearly twice the potency of procaine.Further investigation (Sekiya & Vaughan Williams, 1963b, 1965 provided evidence that pronethalol had some central nervous action which merited further study, in particular the depression or abolition of the reflex withdrawal of a limb in response to electric shocks to the skin. The present paper represents an attempt to carry the analysis of this effect a stage further. It was possible that the depression of the reflex responses was related to the local anaesthetic action of pronethalol. On the other hand, an a priori case could be made for its being connected with blockade of P-receptors in the spinal cord, for Bfilbring & Burn (1941) had reported that, in dogs in which the spinal cord and a limb were perfused with separate circulations, adrenaline greatly potentiated the flexor reflex (contractions of tibialis anterior in response to stimulation of the posterior tibial nerve). It was thus conceivable that the depression of the flexor reflex by pronethalol might have involved the removal of a facilitatory influence in the spinal cord mediated by P-receptors, but before any such hypothesis could be entertained a number of other possible explanations for the depression needed investigation. METHODSContractions of the quadriceps were recorded in response to a train of stimuli (0.9 msec duration, 150 shocks/sec) to the skin or to the ipsilateral sciatic nerve, which was crushed and tied peripherally. The limb was immobilized by transfixation of the femur. Tendon jerks were elicited from the other limb by a solenoid-operated hammer, and when both reflexes were recorded simultaneously ball-bearing myographs were employed (Vaughan Williams, 1964). For tests on neuromuscular conduction, contractions of the gastrocnemius muscle were recorded in response to stimuli to the sciatic nerve, which was crushed * British Council Scholar from the University of San Luis Potosi, Mexico.

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