Controversies surrounding erythrocyte sodium-lithium countertransport

BACKGROUNDInterest originally arose in ouabain-insensitive lithium transport across erythrocyte membranes when it was found that lithium could substitue for sodium, either undergoing 1 :1 lithium exchange or 1 :1 sodium-lithium countertransport in a manner that follows Michaelis- Menten kinetics. Elevation of the sodium-lithium countertransport activity in hypertension was first noted in 1980 and found to be a genetically linked phenomenon. This observation has since been confirmed on several occasions and associations with other dieases such as diabetes have been noted. Nevertheless, many unanswered questions remain about the clinical significance of disturbed sodium-lithium countertransport and its pathological basis. METHODSTraditional methods for characterizing the sodium-lithium countertransporter have depended on determining differences between lithium fluxes into sodium-rich and sodium-free media. There have been inherent problems in deciding on suitable sodium substitutes. Of the available alternatives, choline has emerged as having advantages over magnesium. Reports in the literature have often failed to take into account varied assay conditions, making comparisons of data from different laboratories difficult A further complexity has been the realization that sodium-lithium countertransport activity incorporates two key elements in the form of Vmax and km. Kinetic studies have shown independent variation in these two parameters with various disease states. RESULTSMuch of the published work to date has continued to rely on measurement of countertransport activity, with magnesium acting as the predominant sodium-substitute. This has occurred despite the undoubted benefits obtained from kinetic analysis. Where kinetics of the sodium-lithium countertransporter have been determined, there have emerged clear associations between Vmax and environmental influences such as plasma lipids with elevated values in dyslipidaemic states including diabetes. The affinity constant, km, is more clearly under genetic control and has independent associations with vascular disease. CONCLUSIONSStudy of the erythrocyte sodium-lithium countertransporter has revealed interesting relationships between altered behaviour of the transporter and specific disease states. Although still somewhat of an enigma, this transporter is emerging as an important membrane constituent whose further study may help us to understand the molecular mechanisms leading to vascular disease.