La influencia de Nietzsche en el penmiento de Cioran

The observation that there is an optimal muscle length (Lq) for maximal isometric force production below or beyond which force declines, has been made more than a hundred years ago (Heidenhain, 1864; Blix, 1985). In 1940, Ramsey and Street observed that the maximal isometric force (Fq when

semitendinosus frog fibres occurred at the fibre’s resting length. Calculations based on the lengths of the myofilaments in frog muscle show a resting sarcomere length of 2/jm. At shorter or longer lengths Fo declined. There was a nearly linear drop in Fq with increasing fibre length beyond Lq and a nearly exponential drop with reducing the length below Lq. Force development dropped to zero when the fibre was stretched to twice its Lq.

In 1954 the sliding filament theory was proposed, based on the observation that the length of the myofilaments did not change appreciably during muscle shortening (Huxley and Hanson, 1954; Huxley and Niedergerke, 1954). According to the sliding filament theory, changes in sarcomere or muscle (fibre) length are due to sliding of the thin and thick filaments relative to each other and not due to changes in the lengths of these filaments. Huxley and Niedergerke (1954), trying to provide a possible explanation to Ramsey and Street’s observations, suggested that the linear drop in Fq at lengths greater than Lq could be explained, if Fq was proportional to the amount of overlap between thin and thick filaments within each half-sarcomere. This would require that the force generated by active sites, acting independently of one another, be uniformly distributed along the zone of overlap of the thin and thick filaments. It would therefore be expected that isometric force would drop down to zero, at preparation lengths where there is no overlap between the myofilaments. According to this explanation, the sarcomere length at which isometric force would be expected to drop to zero with extension beyond Lq,

(i.e. the length at which the filaments would not overlap any more), could be calculated as the sum of length of the thick filament plus twice the length of

the thin filament (plus twice the Z-line width). These calculations however, predicted a shorter length than that observed by Ramsey and Street. Huxley and Peachey (1959, 1961) found the sarcomere striation spacing not to be uniform along the length of stretched frog fibres, with sarcomeres near the ends of the fibres being shorter than those in the middle. During an isometric contraction the shorter sarcomeres near the ends of the fibre could generate more force than the more elongated ones in the middle, resulting in further stretching of the latter. In this way the isometric force developed by the shorter end-sarcomeres and consequently the fibre’s Fq, was greater than that expected

based on the fibre’s average sarcomere length. It was also found that a sarcomere would not shorten, when its length exceeded a critical value of 3.5

jum. Measurements of the lengths of the thick and thin filaments showed that 3.5 /jm is the sarcomere length at which filament overlap would be lost, confirming Huxley and Niedergerke’s (1954) original hypothesis. At the same time the difficulty of reliable isometric force measurement due to the sarcomere length non-uniformities and the consequent creeping up of force became apparent.

Using gold leaf markers, Gordon et al (1966) marked a short segment in each of the isolated frog fibres that they used, within which sarcomere length was uniform. The distance between the two markers was continuously measured during the contraction via a ‘spot follower’ device and it was maintained constant via a servomotor. In this way they restricted, but not completely eliminated the creep phase of force development. They did not however use the maximal force developed during a tetanus to determine the force-length

relation, as it would be affected by the creep phenomenon. Instead, they used extrapolation to predict the maximal isometric force at the beginning of the tetanus eliminating the effects of creep. Their results showed that there were four main regions in the force-sarcomere length relationship of the frog. A narrow ‘plateau region’ (sarcomere lengths 2.00-2.25 pm) at which force is optimal. A ‘descending limb’ was observed at longer sarcomere lengths (2.25- 3.65 pm) at which force declines linearly with sarcomere length and reaches zero at that sarcomere length where filament overlap was expected to have just been lost. This was in agreement with the original explanation that Huxley and Niedergerke (1954) attempted to provide to account for Ramsey and Street’s results. At sarcomere lengths between 1.67- 2.00 pm, isometric force also declined linearly with the reduction in sarcomere length. An even steeper linear decline was observed at sarcomere lengths shorter than 1.67 pm with the force reaching zero at a sarcomere length equal to 1.27pm. This part of the force-length relationship, at which force declined from its optimal value with sarcomere length reduction is called the ‘ascending limb’. The causes of isometric force reduction in the ‘ascending limb’ may be related to a reduction in active force production and/or to internal forces opposing shortening (for more details see Rassier et al, 1999 for review).

The force length relationship reported by Gordon et al (1966) holds for frog muscle fibre sarcomeres. Although the length of myosin filaments is remarkably well conserved amongst species, this is not the case with the thin filament lengths and therefore a shift in the force-length relationship would be expected (see Woledge et al, 1985; Rassier et al, 1999). A human force-

sarcomere length relationship would be expected to be shifted, as actin filaments from human muscle are 0.32 /mi longer than in frog muscle (Rassier

et ah 1999).