Intracellular H⁺ buffers protect cells from changes in intracellular pH (pH_i) but also dramatically reduce H⁺ mobility by two orders of magnitude. Such low H⁺ diffusibility may lead to the formation of pH_i microdomains. In ventricular myocytes, which exhibit strong pH_i-dependence of excitation-contraction coupling, and complex pH_i-Ca²⁺ interactions, pH_i non-uniformity will pose a threat to whole-cell homeostasis. In the myocardium, variation in capillary perfusion or metabolic rate, can produce cell-to-cell variation of pH_i and reduce the efficiency of heart function. In the pathological condition of ischaemia, sharp gradients of pH_i may exist at border zones and coincide with areas of abnormal Ca²⁺ signalling. Ventricular myocytes express a considerable concentration of cytoplasmic, low-molecular weight H⁺ buffers, such as dipeptides. These compete for H⁺ with the larger buffer molecules like proteins. They serve as mobile carrier molecules that facilitate H⁺ movement within and between cells, producing a passive H⁺ shuttle mechanism. Near resting pH_i, H⁺-shuttling will keep the interior of cells well-coupled with the sarcolemma, the site of transmembrane acid/base transport. They will also dissipate local acid/base-loads released from subcellular structures such as mitochondria. In coupled cells of the intact myocardium, carrier molecules are able to facilitate H⁺-flux between cells through open gap junctional channels. The ability of such molecules to spatially regulate pH_i inside the myocardium is limited by the fraction of H⁺-buffering that is mobile and by the gating of gap junctions. The former rises with pH_i and is augmented by the addition of exogenous mobile buffers, such as CO₂/bicarbonate. Gap junctional gating can be controlled by a plethora of factors such as phosphorylation, Ca²⁺-dependent proteins and pH_i. Interestingly, both acidosis and alkalosis have been shown to close gap junctions, creating a range of pH_i, defined as the permissive range, over which the junctional route for H⁺-flux is large, and will exceed sarcolemmal acid/base transport if the pH_i disturbance driving junctional flux is local. These findings illustrate a novel paradigm in pH_i regulation, in which the spread of H⁺, carried on shuttles, is determined by the magnitude of the acid/base disturbance. Within the permissive range, cell-to-cell pH_i variation is minimised to help coordinate pH_i-sensitive processes across the myocardium. Outside this range, gap junctions prevent the spread of the local pH_i disturbance and sarcolemmal transporters are recruited remove the excess acid or base from the pH-disturbed cell. The concepts of H⁺-shuttles and their permeation across gap junctions add a new dimension to our understanding of pH_i regulation and may offer new insight into disease conditions in which pH_i changes are a characteristic feature.