Step 1: Ask what the brainstem breathing centre is most sensitive to under normal conditions. Step 2: Central chemoreceptors near the medulla monitor the carbon dioxide level indirectly by detecting the hydrogen ions it forms in the cerebrospinal fluid, making CO$_2$ the dominant driver of ventilation. Step 3: A small rise in CO$_2$ triggers faster and deeper breathing to expel it and restore pH, confirming carbon dioxide as the main stimulus. Step 4: Low oxygen only becomes a meaningful backup drive at very low levels via peripheral sensors, and calcium plays no role here, so the answer remains carbon dioxide. \[\boxed{\text{Carbon dioxide}}\]