Differential regulation of sodium pump isoforms in heart.

Abstract

Abstract We have summarized our studies on regulation of Na + ,K + -ATPase isoforms in heart from four different clinical conditions: hypothyroid, hyperthyroid, hypokalemia, and hypertension. We find they are all characterized by regulation of α2, and only in the hypothyroid is there any change in α1 expression. Perhaps this is not surprising in light of the fact that α1 is the ubiquitous sodium pump, presumably responsible for maintenance of intracellular electrolytes in all tissues, whereas α2 is expressed in a tissue-specific manner suggesting a differentiated function in heart distinct from that of α1. In skeletal muscle, where α2 pumps greatly predominate relative to α1, we describe a homeostatic mechanism responsible for transferring K + from the intracellular to extracellular compartment that is dependent on the decreased expression of α2. The observations discussed here demonstrate that various unrelated pathological conditions are associated with altered expression of cardiac isoforms, and thus ratio of Na + ,K + -ATPase isoforms. Both pre- and posttranslational sites of regulation appear to be involved in the changes in abundance of the isoforms. Targets for pretranslational regulation are likely to reside in sequences governing transcription, whereas translational and posttranslational regulation are quite different and poorly understood. We have suggested in this review that competition of newly synthesized α1 and α2 for assembly with β could be a powerful mechanism responsible for some of the changes unrelated to changes in mRNA levels. Because no ionic, hormonal, or physical signals have been identified as directly involved in the altered expression of sodium pumps, we must consider the possibility that changes in sodium pump expression are secondary, eg, to regulation of another ion transport pathway such as the Na/Ca exchanger, or an ion channel, or of another hormone or receptor such as catecholamines or their receptors (reviewed in reference 39). In order to understand the role of change in expression of sodium pump isoforms in pathological conditions, future work must be aimed at understanding the pattern of regulation of key Na + , K + , and Ca ++ transporters in various pathological states.