[Frontiers in Bioscience 10, 2373-2396, September 1, 2005]

NEURONAL FUNCTION AND ALPHA3 ISOFORM OF THE Na/K-ATPase

Maxim Dobretsov 1, and Joseph R. Stimers 2

1 Department of Anesthesiology and 2 Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Physiological roles of the Na/K-ATPase in nervous system
3.1. Intracellular ion concentrations
3.2. Electrogenic effects
3.3. Extracellular K+ clearance
3.4. Conclusion
4. Multiple isoforms and "neuronal", a 3 isoform of the Na/K-ATPase
4.1. Discovery and neuron-specific expression of a 3 Na/K-ATPase
4.2. Phylogenetic preservation of a 3 Na/K-ATPase
4.3. Ontogenesis and a 3 Na/K-ATPase
4.4. Conclusion
5. Functional identification of neurons with a 3 Na/K-ATPase
5.1. Central nervous system
5.2. Peripheral nervous system
5.3. Stretch receptor
5.4. Conclusion
6. Hypotheses on functional role of neuron-specific expression of the a 3 Na/K-ATPase
6.1. a 3 Na/K-ATPase as a "reserve" pump
6.2. Sub-cellular targeting and compartmentalization of a 3 Na/K-ATPase
6.3.a 3 Na/K-ATPase as a receptor for endogenous compounds
6.4. Transcriptional regulation
6.5. Conclusion
7. Conclusion and perspective
8. Final remarks
9. Acknowledgments

10. References

1. ABSTRACT

The Na/K-ATPase is a complex of integral membrane proteins that carries out active transport of sodium and potassium across the cell plasma membrane, and maintains chemical gradients of these ions. The alpha subunit of the Na/K-ATPase has several isoforms that are expressed in a cell type- and tissue-dependent manner. In adult vertebrates, while kidney cells express mostly alpha1, muscle and glial cells - alpha1 and alpha2, and sperm cells - alpha1 and alpha4 isoforms of Na/K-ATPase, neurons may express alpha1, alpha2, alpha3 or any combination of these isoforms, and evidence suggests that neuronal type is the determining factor. The functional significance of multiple isoforms of the Na/K-ATPase and their non-uniform expression, and the link between neuron function and expression of a given isoform of the Na/K-ATPase in particular, remains unknown. Several hypotheses on this account were introduced, and in this work we will review the present status of these hypotheses, and their standing in application to recent data on the expression of isoforms of the Na/K-ATPase in the peripheral nervous system of vertebrate animals.