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In their journey from the male to the female reproductive tract, spermatozoa are confronted with a constantly changing environment. To cope with the associated challenges, spermatozoa express a distinct set of transporters, channels and pumps. One of the membrane proteins unique to spermatozoa is the α4 isoform of the Na+,K+- ATPase. In addition to α4, spermatozoa express the ubiquous α1 variant. To get a detailed understanding of how α1 and α4 differ, and why spermatozoa need an additional Na+,K+- ATPase, we have conducted an electrophysiological comparison of the rodent isoforms (rat α4 versus mouse α1-3) using the Xenopus oocyte expression system. We demonstrate isoform-specific differences in the voltage sensitivity of steady-state turnover, with α2 being the more sensitive, and α1 and α2 having faster Na+ release kinetics than α3 and α4. Our data further show that the α1 and α2 turnover rates are fast compared with those of α3 and α4. Finally, α4 is less influenced by changes in extracellular Na+ and temperature than α1. Based on these findings, we discuss the possibility that evolution has selected robust activity rather than rapid turnover for α4. [ABSTRACT FROM AUTHOR]

The Na,K-ATPase, or sodium pump, is well known for its role in ion transport across the plasma membrane of animal cells. It carries out the transport of Na ions out of the cell and of K ions into the cell and thus maintains electrolyte and fluid balance. In addition to the fundamental ion-pumping function of the Na,K-ATPase, recent work has suggested additional roles for Na,K-ATPase in signal transduction and biomembrane structure. Several signaling pathways have been found to involve Na,K-ATPase, which serves as a docking station for a fast-growing number of protein interaction partners. In this review, we focus on Na,K-ATPase as a signal transducer, but also briefly discuss other Na,K-ATPase protein-protein interactions, providing a comprehensive overview of the diverse signaling functions ascribed to this well-known enzyme. [ABSTRACT FROM AUTHOR]

At least 5% of individuals with hypertension have adrenal aldosterone-producing adenomas (APAs). Gain-of-function mutations in KCNJ5 and apparent loss-of-function mutations in ATP1A1 and ATP2A3 were reported to occur in APAs. We find that KCNJ5 mutations are common in APAs resembling cortisol-secreting cells of the adrenal zona fasciculata but are absent in a subset of APAs resembling the aldosterone-secreting cells of the adrenal zona glomerulosa. We performed exome sequencing of ten zona glomerulosa-like APAs and identified nine with somatic mutations in either ATP1A1, encoding the Na+/K+ ATPase α1 subunit, or CACNA1D, encoding Cav1.3. The ATP1A1 mutations all caused inward leak currents under physiological conditions, and the CACNA1D mutations induced a shift of voltage-dependent gating to more negative voltages, suppressed inactivation or increased currents. Many APAs with these mutations were <1 cm in diameter and had been overlooked on conventional adrenal imaging. Recognition of the distinct genotype and phenotype for this subset of APAs could facilitate diagnosis. [ABSTRACT FROM AUTHOR]