MedSci 205: Lecture 26 - Energetics of Muscle Fatigue Flashcards
Muscle Fatigue
Failure to maintain the required, or expected, power output, leading to reduced muscle performance.
Mechanisms Leading to Fatigue
Exhaustion fatigue occurs at the intersection of the red and dotted lines on graph of (force of power vs time showing max and required outputs)
Alterations in time take. To fatigue will occur with:
Increase or decrease in required force.
Increase or decrease in maximum force muscle can produce.
Changes in the intrinsic fatiguability of muscles. (Moves final downwards slope of graph to the left or right.)
Where Does Fatigue Occur?
CNS command.
Motor Neuron Signal.
Neuro-Muscular Transmission.
Muscle Fibre AP.
Sight of Fatigue at the Cellular Level
T-tubule Depolarisation.
Signal Open to SR Ca2+ channels.
Ca2+ Release from SR.
Ca2+ binding to Troponin-C.
Cross-bridge attachment.
Force and/or Power Generation by Cross-bridges.
Central Fatigue
Decreased activation from CNS.
Decreased number of motor units required.
Peripheral Fatigue
Affects the cellular mechanisms that control force.
Smaller Ca2+ transient.
Reduced Ca2+ sensitivity of the myofilaments.
Slower cross-bridge cycling.
Proposed Causes of Peripheral Fatigue
Accumulation of metabolites.
Depletion of muscle energy supplies (eg. Glycogen).
How is Fatigue Studied?
- Trained athlete.
- Exercising volunteer subject (sedentary vs active).
- Experimental animal.
- Isolated whole muscle.
- Isolated single fibre (myocyte).
- Contractile proteins in a test tube.
Temporal Summation
Transmission of signals with increased frequency of impulse thus increasing the strength of signals in each fibre.
Effect generated by a single Neuron as a way of achieving an AP.
Time constant is sufficiently long (a fraction of a second) and frequency of rises in potential are high enough that a rise in potential begins before the previous one ends.
Amplitude of previous potential at point where second begins will summary, generating a potential that is overall larger than individual potentials.
Allows for potential to reach the threshold to generate an AP.
~10Hz
Unfused Tetanus
~25Hz
AKA incomplete tetanus.
Relaxation time between successive twitches will get shorter as the strength of contraction increases in amplitude.
Wavy line on graph that is at high point.
Fused Tetanus
~50Hz
Decreased time between twitches causing a state of sustained muscle contraction with a lack of relaxation periods.
Individual muscle twitches are at such a high freq that they are fused and cannot be distinguished from each other.
AKA tonic spasm and tetany.
Possible Actions of Inorganic Phosphate
“Direct” inhibition of rotation of the actomyosin cross-bridge.
Effects (direct or indirect) on Ca2+ release and Ca2+-force dependence (reduced Ca2+ release and increase in Ca2+ force activation threshold)
“Indirect” energetic effect including:
Reduction of free energy of ATP hydrolysis.
May (or may not) affect contraction.
Indirect Action of Inorganic Phosphate
Reduction of the free energy of ATP hydrolysis.
Change in G(ATP) = Change in G(0) + RTln x ([ADP][P] / [ATP])
Effects of Decreased pHi
Competition of H+ with Ca2+ for binding sites on Troponin-C leading to right shift of the Force-[Ca2+]i relationship.
Depression of the Force-[Ca2+]i relation.
Reduced Ca2+ release from the SR.
Major Mechanisms that Contribute to Muscle Fatigue
Voltage sensor activation.
Transmission of the surface membrane AP.
Inward conduction of the TT AP.
SR Ca2+ reuptake.
SR Ca2+ release by RyR.
Ca2+ sensitivity of myofibrilar proteins.
Maximum Ca2+ activated force.
Shortening Velocity.
