RESEARCH ARTICLE The Regulation of Troponins I, C and ANP by

Hibernation is an adaptive strategy used by various mammals to survive the winter under situations of low ambient temperatures and limited or no food availability. The heart of hiber-nating thirteen-lined ground squirrels (Ictidomys tridecemlineatus) has the remarkable abili-ty to descend to low, near 0°C temperatures without falling into cardiac arrest. We hypothesized that the transcription factors GATA4 and Nkx2-5 may play a role in cardiopro-tection by facilitating the expression of key downstream targets such as troponin I, troponin C, and ANP (atrial natriuretic peptide). This study measured relative changes in transcript levels, protein levels, protein post-translational modifications, and transcription factor bind-ing over six stages: euthermic control (EC), entrance into torpor (EN), early torpor (ET), late torpor (LT), early arousal (EA), and interbout arousal (IA). We found differential regulation of GATA4 whereby transcript/protein expression, post-translational modification (phosphory-lation of serine 261), and DNA binding were enhanced during the transitory phases (en-trance and arousal) of hibernation. Activation of GATA4 was paired with increases in cardiac troponin I, troponin C and ANP protein levels during entrance, while increases i