Cellular Pharmacology of Lanthanum

The general chemical characteristics of the rare earth or lanthanide series of ele­ ments resemble those of the alkaline earth elements in many respects (I). Of the lanthanides, lanthanum has long been considered to have chemical properties most similar to the alkaline earths (2). Recent interest in the biological actions of lan­ thanum ion (LaH) is almost entirely based upon use of this rare earth ion as a substitute or antagonist for Ca2+ in a variety of cellular and subcellular reactions. The rapid and widespread employment of LaH in the last few years is a measure of the complex and varied functions of Ca2+ in membrane and coupling reactions. In this review article, I attempt to concentrate upon the cellular actions of LaH in muscle, nerve, and related tissues. A considerable literature has also accumulated concerning use of LaH to discern the presence or absence of anatomical barriers and to delineate the molecular nature and specificity of subcellular Ca2+ transport systems and membrane structure. References to these areas of research (as well as to the general pharmacology of LaH) will be limited to those studies most relevant to a consideration of the cellular basis of the actions of LaH. As long ago as 1910, Mines (3) examined the inhibitory effects of LaH upon contractile function in frog heart. However, the recent proliferation of LaH-related studies can quite clearly be traced to a prediction in 1964 by Lettvin and co-workers (4) that LaH, by virtue of an ionic radius similar to Ca2+ and a higher valence than Ca2+, will bind at superficially located Ca2+ sites in a less reversible manner than does Ca2+. The subsequent testing of this prediction (5) demonstrated that La3+ did indeed exert a blocking action in lobster axons and that it acted in a manner equivalent to an extremely high Ca2+ concentration. The high affinity of LaH for membrane binding sites was of particular interest when related to evidence that the distribution of LaH in many different preparations was confined to membrane areas contiguous with the extracellular space (6-12). Thus, use of LaH as a relatively specific Ca2+ substitute or antagonist at well-defined