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Inherited and Phenotypically Plastic Characteristics of Cardiac and Skeletal Muscle Physiology in Mice Selectively Bred for High Voluntary Wheel Running

Abstract

Directional selection for a physiological trait may either change the innate physiology or increase the plasticity seen in the response to selection. The response of individuals to exercise training can be considered a plastic response while innate differences that increase performance may reflect changes in the genome that have occurred due to directional selection. This dissertation examined changes that could occur in cardiac and skeletal muscle, either innately or due to training, that may affect exercise performance using mice that are selectively bred for high voluntary wheel running.

Chapter one examined whether changes in electrocardiogram (ECG) characteristics are innate or if they differ between the high runner (HR) and control (C) lines with training. We used a non-invasive method of recording ECGs through the foot pads of conscious mice before and after access to running wheels for six days. Heart rate decreased in all mice after wheel access, but this effect was larger in the HR mice. PR interval duration increased in HR mice after wheel access and the QRS complex was increased in a subset of the HR mice known as the mini-muscle phenotype.

Chapter two examined whether mice from HR lines have increased ability to resist or recover from contusion or exercise-induced muscle injury. For contusion injury, male mice were anesthetized and a ball bearing was dropped onto the triceps surae muscle, and wheel running was measured for six days post-injury. For exercise-induced injury, male mice were housed for 6 days with or without wheel access and then evaluated for muscle injury and regeneration using histological and circulating markers. Control and HR mice respond similarly to contusion injury, both reducing wheel running. HR mice show increased central nuclei (a marker of regeneration) in the soleus muscle and mini-muscle mice show increases in regeneration and injury in the deep and superficial gastrocnemius.

Chapter three examined the buffering capacity of thigh muscles of mice housed either with or without wheels for 6 days. Female mice had lower buffering capacity than males, and mini-muscle mice had lower buffering capacity than normal-muscled individuals. Wheel running had no effect on the buffering capacity.

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