Potassium loss during myocardial ischaemia and hypoxia: does lactate efflux play a role?

In heart, the available evidence suggests that transmembrane lactate flux is mediated predominantly by an H(+)-lactate transporter with properties similar, but not identical, to the H(+)-monocarboxylate transporter present in many other tissues. Passive (electro-)diffusion of HL and L- comprise only minor components of total transmembrane lactate flux over the range of lactate concentrations relevant to normal physiological and pathophysiological states. The cardiac H(+)-lactate transporter is non-electrogenic, and transport is partially inhibited by potassium, possibly by competition for the H+ binding site on the carrier. However, K+ is cotransported with lactate very inefficiently, if at all, compared to H+. From these observations, a direct mechanism coupling potassium efflux to lactate efflux, by either an electrogenic or a non-electrogenic mechanism, is unlikely to account for the majority of net potassium loss during myocardial ischaemia or hypoxia, unless the properties of transmembrane lactate flux are markedly altered by the ischaemic and hypoxic environment. Nevertheless, it is intriguing that alterations in pHi, pHo, and transmembrane pH gradients in ischaemic cardiac muscle and fatigued skeletal muscle have effects on net potassium loss that qualitatively parallel the predicted effects on L- efflux. In view of the lack of evidence for a direct link between potassium and lactate efflux in the heart, it is likely that this apparent relationship is either coincidental or indirect, mediated through a series of intermediate transport processes. The nature of these interactions remain to be defined. Further studies are still needed to solve the puzzle of what causes net cellular potassium loss during myocardial ischaemia and hypoxia.