Cardiac Adaptation to Heat Acclimation and Exercise Training: Molecular-Physiological Linkage in Force Generation

PURPOSE: Heat acclimation and exercise training induce adaptive changes in the heart, such as decreased resting heart rate, elevated stroke volume and metabolic efficiency. Given the unique metabolic demands of each stressor, these adaptations are achieved differently. Heat acclimation facilitates increased cardiac pressure at a decreased metabolic rate and enhances compliance, whereas the trained heart exhibits hypertrophy. In this study we characterized the emerging physiological and molecular adaptations to these stressors.
METHODS: Male rats, Rattus norvegicus were divided into 4 groups. Sedentary: Normothermic Controls - 24°C (CO) and heat acclimated - 34o C for 30 days (AC). Trained: normothermic (EX) and Acclimated (EXAC) rats were subjected to an increasing exercise load on a treadmill (0.64 m/sec), 1 hr/d, 5 d/week, for 1 month. A cDNA Atlas Array (Clontech Rat 1.2 array) was used to screen the genomic changes. Inward calcium currents (ICa) and action potentials in isolated ventricular cardiomyocytes were determined using a whole cell recording technique. Ca2+transients and contractile force generation in single cells were measured using a Fluorometic apparatus and Edge detector systems, respectively.
RESULTS: Among the 800 genes detected, more were upregulated. The EXAC group expressed the smallest number of genes. Genes encoding sarcoplasmic Ca2+regulatory proteins, L-type Ca2+channel as well as those associated with K+currents were profoundly upregulated in the heat acclimated hearts. Pathways associated with Ca 2+regulatory proteins, Ca2+signaling and muscle contraction were upregulated in all the groups (albeit differently in each group). The expression of the Ca2+signaling pathways predominated in AC, whereas the expression of the Ca2+regulatory genes was the highest in EXAC. Previous findings of enhanced contractile force in AC and EX together with the variations in genomic responses among the groups, caused us to focus on the contractile properties of the myocytes. ICa were higher in CON and EX than in the AC and EXAC groups. Trained groups generated higher ICa amplitudes vs. sedentary. Concomitantly, a higher Ca2+transient was needed to generate similar contractile forces in groups exposed to heat, suggesting that the myofilaments became less sensitive to Ca2+.
CONCLUSIONS: There is causal evidence for a link between the studied physiological and genomic responses. Therefore different molecular adaptations were used to produce the similar physiological phenotype of increased cytosolic Ca2+concentration.