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Dettbarn, W. D.

Publications and source records attributed to Dettbarn, W. D..

Disuse Induced Changes in the Cholinergic System of Sciatic Nerve and Slow and Fast Twitch Muscle of Rats

Hindlimb suspension was used as a model of disuse in experiments studing the effects of reduced muscle activity on AChE and its molecular forms, choline acetyltransferase and nicotinic receptor binding in innervated slow and fast muscle. The weight of SOL was reduced to 64% within one week and continued to decrease progressively up to the third week when the weight was reduced to 40% as compared to controls. EDL showed a significant decrease in its weight only at the end of three weeks hypokinesia when it was reduced to 71% of control. Biochemical and histochemical findings are summarized. From these data and from morphological findings it is evident that some properties of skeletal muscles are strongly dependent on patterns and level of loadbearing and on motor unit activiy. With suspension-induced disuse, the usually slow SOL appeared to change its characteristics such as fiber type distribution and AChE activity to one that more resembled a faster muscle. It is important to note that hypokinesia induced changes either physiological, biochemical or morphological, are totally reversible as the induced changes returned to control levels within a week after cessation of disuse.

Dettbarn, W. D.↗

Is fast fiber innervation responsible for increased acetylcholinesterase activity in reinnervating soleus muscles?

An investigation was conducted as to whether the predominantly slow SOL, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the EDL. Local denervation of the SOL in the guinea pig was performed because this muscle is composed solely of slow (type I) fibers; thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innvervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the SOL. It is concluded that the neural control of AChe is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle.

Misulis, K. E.↗

Use and disuse and the control of acetylcholinesterase activity in fast and slow twitch muscle of rat

The role of acetylcholinesterase (AChE) in neuromuscular transmission is relatively well established, little is known, however, of the mechanisms that regulate its synthesis and control its specific distribution in fast and slow muscle. Innervation plays an important role in the regulation of AChE and elimination of the influence of the nerve by surgical denervation results in a loss of AChE. The influences of the nerve and how they are mediated was investigated. It is suggested that muscle usage and other factors such as materials carried by axonal transport may participate in the regulation of this enzyme. The mechanisms that regulate AChE and its molecular forms in two functionally different forms are studied.

Dettbarn, W. D.↗

Differential effect of denervation on free radical scavenging enzymes in slow and fast muscle of rat

To determine the effect of denervation on the free radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the mid-thigh region and the muscle tissue levels of 5 enzymes were studied 2 and 5 weeks following crush. Radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. These data represent the first systematic report of free radical scavening systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle.

Asayama, K.↗

Physiological changes in fast and slow muscle with simulated weightlessness

A rat hindlimb suspension model of simulated weightlessness was used to examine the physiological characteristics of skeletal muscle. The physiological sequelae of hindlimb suspension were compared to those of spinal cord section, denervation by sciatic nerve crush, and control. Muscle examined were the predominantly slow (Type 1) soleus (SOL) and the predominantly fast (Type 2) extensor digitorum longus (EDL). Two procedures which alter motor unit activity, hindlimb suspension and spinal cord section, produce changes in characteristics of skeletal muscles that are dependent upon fiber type. The SOL develops characteristics more representative of a fast muscle, including smaller Type 1 fiber proportion and higher AChE activity. The EDL, which is already predominantly fast, loses most of its few Type 1 fibers, thus also becoming faster. These data are in agreement with the studies in which rats experienced actual weightlessness.

Dettbarn, W. D.↗

Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

Gupta, R. C.↗