The renal phenotype induced by loss-of-function mutations of inwardly rectifying potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia, metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.4.1 mutations cause the tubulopathy is not completely understood. Here we demonstrate that Kcnj10 is a main contributor to the basolateral K conductance in the early distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl cotransporter (NCC) in the DCT. Immunostaining demonstrated Kcnj10 and Kcnj16 were expressed in the basolateral membrane of DCT, and patch-clamp studies detected a 40-pS K channel in the basolateral membrane of the DCT1 of p8/p10 wild-type Kcnj10 +/+ mice (WT). This 40-pS K channel is absent in homozygous Kcnj10 −/− (knockout) mice. The disruption of Kcnj10 almost completely eliminated the basolateral K conductance and decreased the negativity of the cell membrane potential in DCT1. Moreover, the lack of Kcnj10 decreased the basolateral Cl conductance, inhibited the expression of Ste20-related proline-alanine-rich kinase and diminished the apical NCC expression in DCT. We conclude that Kcnj10 plays a dominant role in determining the basolateral K conductance and membrane potential of DCT1 and that the basolateral K channel activity in the DCT determines the apical NCC expression possibly through a Ste20-related proline-alanine-rich kinasedependent mechanism. SeSAME/EAST syndrome | Kir.5.1 | SPAK | WNK T he distal convoluted tubule (DCT) of the kidney is responsible for the absorption of 5% of the filtered NaCl load and plays an important role in the reabsorption of Ca 2+ and Mg 2+

Transmission of Chlamydia trachomatis and Neisseria gonorrhoeae among infected men and their female sex partners was examined using a design enhancing the likelihood that spread was directed from men to women. Chlamydia culture-negative specimens were examined using DNA amplification tests. Infection rates in women exposed to male sex partners with Chlamydia only were 65% (20/31) and with gonorrhea only were 73% (33/45). Infection of women by either agent was not influenced by the number of sexual exposures to or coinfection in men. There was a 98% (40/41) concordance of N. gonorrhoeae isolates among partners by auxotype and serovar. Chlamydia isolates were serotyped using ELISA and immunofluorescence testing and confirmed by nested polymerase chain reaction: 50% (6/12) of men and 57% (8/14) of women yielded mixed serovars. Sixty-four percent of pairs (9/14) were infected with identical serovars and an additional 28% shared at least one serovar. Multiple serovars of C. trachomatis, but not of N. gonorrhoeae, were common in sex partners and exchanged frequently.