GJA1 and ischemia: As results, vagal stimulation and ACh have been shown to 1) prevent the loss of functional gap-junction channels and protect hearts against ischemia-induced lethal arrhythmias [4], 2) protect cardiomyocytes against hypoxia through the PI3K/Akt/HIF-1α pathway [5], 3) keep cell-cell communication by preserving the gap-junction protein level during hypoxia through inhibition of the connexin 43 degradation pathway [34], and 4) prevent a reperfusion-induced collapse in mitochondrial transmembrane potential by inhibition of mitochondrial permeability transition pore opening [35].