VOL. 4 (1950) CONTRACTILITY OF A NON-CONDUCTING FIBER 65 



CaClg or MgClg in various concentrations. Fibers which contracted as little as 20% of 

 initial length were not restored to their original length. Relaxation may be a more 

 complicated process than contraction depending on the integration of several reactions 

 performed poorly, if at all, in this preparation. That ATP induces contraction and not 

 relaxation of the fibers does not indicate at which phase of contraction dephosphoryla- 

 tion of ATP occurs^^. 



It has been observed that fibers inhibited from contraction by o-iodosobenzoate 

 and then exposed for 2 minutes to ATP did not regain their contractility after prolonged 

 washing in cysteine saline. This may indicate a reaction of ATP with proteins of the 

 fiber possibly independent of that initiating contraction. This observation may offer 

 an explanation for the inability of the fibers to relax, since in the usual experiments 

 performed to measure isotonic contraction, the fibers were exposed to ATP for Deriods 

 longer than 2 minutes. 



It is noteworthy that the contraction of the fibers produced by ATP is enhanced 

 by the addition of magnesium ions. This effect finds its analogy in the action of this 

 ion in increasing the adsorption of ATP by actomyosin^^. The magnitude of the effect 

 and the optimal concentration of magnesium ion at which it occurs are in harmony 

 with similar observations in isolated ATP-actomyosin systems. 



Activation of the fiber contraction by magnesium contrasts to its depressing effect 

 on the intact muscle^". Further observations are necessary to decide whether this may 

 indicate that the magnesium effect in the intact fiber is due to an action on the conduc- 

 tive membrane. 



Compounds like mapharsen and o-iodosobenzoate which reversibly inhibited contrac- 

 tion of the fibers inactivate ATPase activity of myosin^i. The inhibitors are not specific 

 for ATPase but rather oxidize or combine with thiol groups in general. By measuring 

 the ATPase activity of the homogenates of the fibers, one may secure an index of their 

 efficacy in affecting available -SH groupings. However, the inactivation of ATPase may 

 not be directly correlated with the ability of these inhibitors to prevent contraction. 

 The sulfhydryl groups binding actin to myosin, e.g., are susceptible to effects of these 

 inhibitors-^. The loss of fiber contractility may be related to a stabilization or blocking 

 of sulfhydryl linkages of the contractile proteins themselves. 



By means of the elemental contractile system under study, the action of the bio- 

 logically important compounds listed in Table IV can be further differentiated. All the 

 substances enumerated are known to affect the process of contraction of intact muscle 

 fibers. Since they are ineffective in influencing fiber contraction produced by ATP, their 

 site of action may be assumed to be elsewhere. From data available it is probable that 

 they affect contraction of intact fibeis through their action on the conductive membrane 

 of the muscle either at the neuromuscular junction or along the fibers. Of particular 

 interest in this connection is the absence of any effect of the cholinesterase inhibiting 

 compounds, such as diz'sopropylfluorophosphate and eserine, on the contractile process. 

 This does not support the assumption of a general toxic effect of these compounds as 

 proposed by some investigators, but is consistent with the view which attributes their 

 effect to blocking conductions^. 



The observations presented show the usefulness of the non-conductive contractile 

 preparation of muscle described by Szent-Gyorgyi. The system simplifies the study 

 of the contractile process and offers an opportunity to study chemical and pharmaco- 

 logical factors affecting contraction as distinct from conduction. 

 References p. 6y. 



