Molecular Aspects of Thermal Tolerance and Exertional Heat Illness Susceptibility

  • Elaine C. LeeEmail author
  • Jacob S. Bowie
  • Aidan P. Fiol
  • Robert A. Huggins


Thermoregulation includes many physiological, molecular/cellular, and genetic mechanisms that are highlighted in Chap.  2. Molecular and cellular mechanisms of thermal tolerance (on a whole-body level) and relationships to EHS (exertional heat stroke) susceptibility include pathways associated with immune, endocrine, antioxidant, metabolic, skeletal muscle, and nervous system function. Research clearly implicates pathophysiology arising from LPS (lipopolysaccharide)-induced TLR4 (toll-like receptor 4) activation and subsequent endotoxemia/sepsis-induced inflammation and tissue damage. However, the role is not clearly defined because many have not considered the vast complexity in LPS and TLR-associated positive feedback to inflammation. We present aspects of immune function that complicate the relationship between endotoxemia and EHS pathophysiology that should be studied in future research and make it difficult to associate immune-related genotypes with EHS risk. Additionally, we present molecular targets of pharmacological treatments and individual genotypes associated with susceptibility to heat stress and MH (malignant hyperthermia) to depict novel molecular mechanisms likely associated with pathophysiology and EHS susceptibility.


Thermal tolerance Malignant hyperthermia Endotoxemia Ryanodine receptor Calcium signaling TRPV1 Calsequestrin 


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Authors and Affiliations

  • Elaine C. Lee
    • 1
    • 2
    Email author
  • Jacob S. Bowie
    • 1
    • 2
  • Aidan P. Fiol
    • 1
    • 2
  • Robert A. Huggins
    • 1
    • 2
    • 3
  1. 1.Human Performance Laboratory, Department of Kinesiology, University of ConnecticutStorrsUSA
  2. 2.Department of KinesiologyUniversity of ConnecticutStorrsUSA
  3. 3.Korey Stringer Institute, Department of Kinesiology, University of ConnecticutStorrsUSA

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