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Many effects of pH on contraction in the heart are mediated through actions on the myofilaments and the Ca2+-binding protein, troponin C. Many other effects, however, are mediated through modulatory actions on intracellular Ca2+ signalling. We are investigating these actions, which are complex and often appear paradoxical. For example, acidosis initially depresses the Ca2+ transient that triggers contraction, but later on it can profoundly enhance the transient. Much of this latter effect forms the basis of the so-called “pH-paradox” that occurs during post ischaemic reperfusion of the heart.  The scenario is that intracellular acid overload leads to intracellular Ca2+ overload and the appearance of triggered arrhythmias. A major part of the effect is mediated through overdrive of the acid extrusion proteins NHE and NBC, as inhibiting the transporters pharmacologically prevents much of the Ca2+overload and suppresses the arrhythmia. Selective inhibition of these transporters appears to be cardioprotective during post ischaemic reperfusion in animal models.