Drugs that inhibit Na,K-ATPases, such as digoxin and ouabain, alter cardiac myocyte contractility. We recently demonstrated that agrin, a protein first identified at the vertebrate neuromuscular junction, binds to and regulates the activity of ␣3 subunit-containing isoforms of the Na,K-ATPase in the mammalian brain. Both agrin and the ␣3 Na,K-ATPase are expressed in heart, but their potential for interaction and effect on cardiac myocyte function was unknown. Here we show that agrin binds to the ␣3 subunit of the Na,K-ATPase in cardiac myocyte membranes, inducing tyrosine phosphorylation and inhibiting activity of the pump. Agrin also triggers a rapid increase in cytoplasmic Na ؉ in cardiac myocytes, suggesting a role in cardiac myocyte function. Consistent with this hypothesis, spontaneous contraction frequencies of cultured cardiac myocytes prepared from mice in which agrin expression is blocked by mutation of the Agrn gene are significantly higher than in the wild type. The Agrn mutant phenotype is rescued by acute treatment with recombinant agrin. Furthermore, exposure of wild type myocytes to an agrin antagonist phenocopies the Agrn mutation. These data demonstrate that the basal frequency of myocyte contraction depends on endogenous agrin-␣3 Na,K-ATPase interaction and suggest that agrin modulation of the ␣3 Na,KATPase is important in regulating heart function. Na,K-ATPases, or sodium pumps, are integral membrane enzymes found in all animal cells. Using energy from the hydrolysis of ATP they transport three Na ϩ ions out of the cell for every two K ϩ ions into the cell, resulting in a transmembrane chemical gradient that is reflected in the resting membrane potential and used to drive a variety of secondary transport processes. Each Na,K-ATPase is a heterodimer consisting of an ␣-and ␤-subunit. The ␣-subunit is the catalytic subunit and contains the binding sites for Na ϩ and K ϩ . The ␤-subunit is required for pump function and targeting of the ␣-subunit to the plasma membrane. Four ␣-and three ␤-subunit genes have been identified. All combinations of ␣-and ␤-subunits form functional pumps, but developmental, cellular, and subcellular differences in expression suggest functional adaptation of the different isoforms (1).Na,K-ATPases play a central role in regulating the contractile activity of cardiac muscle (2). They are directly responsible for the Na ϩ gradient required for propagation of action potentials that initiate myocyte contraction. Moreover, because of the dependence of the Na ϩ /Ca 2ϩ exchanger (NCX) 3 on the Na ϩ gradient as the source of counterions for transport of Ca 2ϩ out of the cell, they play a critical role in Ca 2ϩ homeostasis and excitation-contraction coupling. For example, inhibition of Na,K-ATPases by digoxin, ouabain, or other cardiac glycoside results in a decline of the Na ϩ gradient, reducing NCX activity and Ca 2ϩ efflux. The inotropic effects of cardiac glycosides result from uptake of this "excess" cytoplasmic Ca 2ϩ into the sarcoplasmic reticulum, raising the level of Ca ...

Purpose of review To review recent developments in the field of gastroduodenal mucosal defense. Recent findings Research in the field of gastroduodenal mucosal defense has focused on continued elucidation of molecular mechanisms that protect the mucosa and influence healing at the cellular level. Review of literature over the past year reveals that familiar proteins and mediators such as nitric oxide, Toll-like receptors, nucleotide-binding oligomerization domain-containing proteins, β-defensins, macrophages, dendritic cells, mucins, autophagy, and the influence of aging and diet are still subjects of study, but also brings into light new processes and mediators such as dual oxidases, defense against radiation injuries, and novel proteins such as ZBP-89. Summary These new published findings contribute to our overall understanding of gastroduodenal defense and suggest innovative avenues of future research and possible novel therapeutic targets.

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Purpose of review-To review recent developments in the field of gastroduodenal mucosal defense.Recent findings-Research in the field of gastroduodenal mucosal defense has focused on continued elucidation of molecular mechanisms that protect the mucosa and influence healing at the cellular level. Review of literature over the past year reveals that familiar proteins and mediators such as nitric oxide, Toll-like receptors, nucleotide-binding oligomerization domaincontaining proteins, β-defensins, macrophages, dendritic cells, mucins, autophagy, and the influence of aging and diet are still subjects of study, but also brings into light new processes and mediators such as dual oxidases, defense against radiation injuries, and novel proteins such as ZBP-89.Summary-These new published findings contribute to our overall understanding of gastroduodenal defense and suggest innovative avenues of future research and possible novel therapeutic targets.

We describe a case in which a patient receiving parenteral nutrition (PN) developed hypophosphatemia. Due to lack of availability of parenteral phosphate supplements, we chose to restore phosphate using diluted hypertonic sodium phosphate enemas. Due to the recent shortages of parenteral minerals and vitamins, such an alternate means of repletion is of increasing importance. Diluted hypertonic sodium phosphate enemas are inexpensive, easy to administer, and effective since phosphate is readily absorbed across the rectal mucosa. We hope that through this type of repletion, life-threatening hypophosphatemia among patients receiving PN can be avoided.