A pH-driven compromise of intracellular Ca2+ signalling in cardiac myocytes can underpin arrhythmogenesis, particularly during myocardial ischaemia, a clinical condition associated with low pHi. Myocardial pHi (normally kept at ~7.20) is spatially regulated via H+-ion chemoreceptors on Cx43 (connexin) protein channels expressed at gap junctions. These receptors acutely regulate Cx-channel opening and closure, resulting in a biphasic dependence of junctional permeability on pHi (maximal permeability at pHi 6.95). High concentrations (10-20mM) of cytoplasmic mobile molecules that reversibly bind H+ ions mediate passive cell-to-cell H+ flux through open Cx channels, in response to local pHi non-uniformity. Cx channels thus regulate spatial variations in myocardial pHi. H+ ions are universal end-products of metabolism. They modulate Ca2+ signalling, electrical rhythm and contractility in the heart. The spatial control of myocardial pHi via Cx channels thus spatially modulates Ca2+i. Key pHi /Ca2+i coupling is mediated by common binding sites on small intracellular molecules, such as carnosine and ATP, as well as via a functional coupling between sarcolemmal Na/Ca and Na/H exchangers. As a result, low pHi triggers a rise of Ca2+i. Furthermore, spatial gradients of pHi, when they occur within cells or in groups of cells, induce local gradients of both diastolic and systolic Ca2+. Depending on the activity of local Na/H exchangers, pHi gradients can also stimulate or suppress spontaneous Ca2+ waves and their local propagation. Ca2+ waves, particularly at border zones, are a common feature of regional myocardial ischaemia. It is likely that a spatial disordering of pHi in the heart provides a key substrate for this Ca2+ heterogeneity, which, in turn, is an important substrate for arrhythmia. When mapping out the clinical causes of arrhythmogenesis, it is therefore necessary to consider the integrated control of both Ca2+ and pH.