FRANK W. BOOTH AND DONALD B. THOMASON Volume
emphasized that biochemical and physiological adapta-tions to a changed environment or physiological stimu-lus fall into two categories based on their duration. Cel-lular, organ, or systemic alterations that occur on thesame time scale as a single exercise bout are said to beacute exercise responses. On the other hand, changes incells, organs, or systems that persist for appreciable pe-riods after or as a consequence of physical training aresaid to be exercise adaptations. A function of exerciseadaptation seems to be to minimize disruption of homeo-stasis during an exercise bout. It is this better mainte-nance of the milieu interieur by the exercise adaptationsthat favors the functional effectiveness of the animalbeyond the resting state. Less disruption in homeostasispermits the animal or human to undergo physical workfor longer durations at the same absolute power beforefatigue. This review considers molecular and cellular re-sponses to exercise that may signal molecular and cellu-lar adaptations during physical training.
B. Signijicance of Adaptations to Exercise
This review is organized to use some of the knowncauses of fatigue during physical exercise as links be-tween molecular and cellular changes that occur as aresult of physical training and the chronic adaptationsthat are characteristic of physical training. One canspeculate that adaptations that improved an animal’swork capacity enhanced its survival. The genetic abilityto alter exercise performance through physical traininghas not been lost along the evolutionary scale. Conse-quently, not all known molecular and cellular changes toexercise are considered here; this is because their func-tion may not yet be recognized to be associated withadaptations that ameliorate fatigue. In addition, thisreview does not repeat in great detail material that isavailable in other reviews. There are 11,689 documentsfor the Medline MESH word “exertion,” Medline’s termfor exercise, between 1984-1989, inclusive. To the readerunfamiliar with the causes of fatigue during physical-exertion, enough description has been given (Table 1) topermit understanding of the physiological significanceof the molecular and cellular events. A more detailedreview on fatigue is available (108). In addition, thereader is referred to earlier reviews that have compre-hensively documented biochemical responses to a singleexercise bout and biochemical adaptations of muscle tophysical training.
C. Causes of Fatigue in Skeletal Muscle DuringPhysical Exercise
Fatigue is defined as the inability of the animal orhuman to continue working at a given exercise intensity.Thus a reduction in power output is seen as fatigue(291). This section briefly delineates how various causesof fatigue (Table 1) prevent an animal or a human frombeing able to continue working at a given rate or level ofactivity. Fatigue mechanisms thus cause an individualeither to exercise at a lower intensity or to stop exercis-ing altogether. The reader is referred to an excellentreview by Gollnick (132) for a more in-depth coverage ofenergy metabolism during prolonged exercise.
I. Adenosine triphosphate depletion
The interaction of the myosin and actin filamentsduring muscle contraction is powered by ATP. Througha complex series of molecular events, energy from thebinding and enzymatic cleavage of ATP to ADP and Pipowers the formation of the myosin-actin cross bridge,conformational translocation of the opposing filaments,and release of the cross bridge to begin the cycle again.Thus each cycle of myosin and actin cross-bridge forma-tion consumes an ATP molecule. Furthermore, the pul-satile increase in sarcoplasmic free Ca2+ during contrac-tion initiates cross-bridge cycling; additional ATP isconsumed in releasing and sequestering Ca2’. New-sholme and Leech (291) speculate that the small de-creases in ATP concentration in skeletal muscle duringan all-out sprint would diminish myosin adenosinetri-phosphatase (ATPase) activity and hence cross-bridgecycling, in turn preventing continued sprinting at thesame pace. Also a decreased ATP concentration woulddecrease Ca2’ cycling and possibly contribute to fatigue.
After continuous high-intensity exercise to exhaus-tion, intramuscular pH can decrease to 6.6-6.3 (171,274,336). In working muscle, the decrease in muscle power(work per unit of time) at low pH is attributed to protoninterference with the catalytic activity of many en-zymes (292). Increased free H+ could produce some, orall, of the following metabolic processes. They are inhibi-tion of phosphofructokinase activity
(74, 135, ZZO),
which would diminish ATP production via glycolysis;decrease of glycogen breakdown by inhibition of phos-phorylase kinase and adenylate cyclase activity and by ashift from HPOZ- to H,PO, (59); decrease in maximumtension due to increased free Ca2’ required to obtain thesame submaximal tension (86); increase in the constantfor. the apparent binding of Ca2’ to troponin (117),thereby attenuating the contractile response (223); anddecrease in Ca2+ release from the sarcoplasmic reticu-lum (289), which would decrease muscle tension. For fur-ther discussions on muscle fatigue, see References 108,153,291,328,336, and 414.Force production by muscle is also reduced by theformation of the diprotonated form of Pi (H,P0,)(295).Because Pi and H+ both increase in muscle undergoingintense exercise, the shift in equilibrium causes force todecrease.
3. Glycogen depletion
A relationship between carbohydrate depletion andfatigue was demonstrated by Christensen and Hansen