Pharmacological and physiological properties of denervated mammalian skeletal muscle.

In the current work the relation between the newly formed, cholinergic membrane receptors and the Ach-induced contracture, the relation between fibrillation and denervation contracture, and the nature of the cholinergic and adrenergic receptors at end-plate-free sites were investigated in the denervated anterior gracilis muscle of the rat. The anterior gracilis muscle of the rat was selected as the test object because it is anatomically suited for the study of the pharmacological characteristics of the newly-formed receptors of endplate-free regions of the denervated muscle. A new microdrop technic was developed for the topical application of 0.5 uml volumes of drug solution to the membrane. Ach sensitivity after denervation develops at a uniform rate over the entire surface of the denervated anterior gracilis muscle. Depolarization is quantitatively related to the concentration of topically applied Ach, and the degree of depolarization is proportional to the magnitude of contracture. Denervation contracture of Ach-stimulated muscle is not the consequence of a massive discharge of a massive discharge of fibrillatory potentials, but is a non-propagated response produced by a persistent, local depolarization. The anterior gracilis muscle is pharmacologically unique because the junctional receptors of the normal muscle and the newly-formed receptors on the end-plate-free regions of the muscle are muscarinic as well as nicotinic in character. Thus, the Ach-produced contracture of the anterior gracilis muscle denervation is the result of the development of both muscarinic and nicotinic receptors over the entire surface of the muscle. In contract to the effects of Ach on the denervated skeletal muscle, catecholamines applied topically do not produce either depolarization or contracture. The only adrenergic response elicited by the topical application of catecholamines is an increase in the rate of discharge of fibrillatory potentials. However, the catecholamines administered intra-arterially produce both depolarization and contracture. Unlike Ach-induced contracture, it does not appear that catecholamine-induced contracture of denervated muscle is the result of the development of new adrenergic receptors on the membrane.