The effect of high-dietary K (HK) on Kir4.1/Kir5.1 and ROMK in the distal convoluted tubule (DCT) is not affected by gender and Cl content of the diet.

Basolateral potassium channels in the distal convoluted tubule (DCT) are composed of inwardly-rectifying potassium channel 4.1 (Kir4.1) and Kir5.1. Kir4.1 interacts with Kir5.1 to form a 40 pS K channel which is the only type K channel expressed in the basolateral membrane of the DCT. Moreover, Kir4.1/Kir5.1 heterotetramer plays a key role in determining the expression and activity of thiazide-sensitive Na-Cl cotransport (NCC). In addition to Kir4.1/Kir5.1, Kir1.1 (ROMK) is expressed in the apical membrane of the late DCT (DCT2) and plays a key role in mediating epithelial Na channel (ENaC)-dependent K excretion. High dietary-K-intake (HK) stimulates ROMK and inhibits Kir4.1/Kir5.1 in the DCT. Inhibition of Kir4.1/Kir5.1 is essential for HK-induced suppression of NCC whereas the stimulation of ROMK is important for increasing ENaC-dependent K excretion during HK. We have now used the patch-clamp-technique to examine whether gender and Cl content of K-diet affect HK-induced inhibition of basolateral Kir4.1/Kir5.1 and HK-induced stimulation of ROMK. Single-channel-recording shows that basolateral 40 pS K channel (Kir4.1/Kir5.1) activity of the DCT defined by NP was 1.34 (1% KCl, normal K, NK), 0.95 (5% KCl) and 1.03 (5% K-citrate) in male mice while it was 1.47, 1.02 and 1.05 in female mice. The whole-cell recording shows that Kir4.1/Kir5.1-mediated-K current of the early-DCT (DCT1) was 1,170 pA (NK), 725 pA (5% KCl) and 700 pA (5% K-citrate) in male mice whereas it was 1,125 pA, 674 pA and 700 pA in female mice. Moreover, K-currents (I) reversal potential of DCT (an index of membrane potential) was -63 mV (NK), -49 mV (5% KCl) and -49 mV (5% K-citrate) in the male mice whereas it was -63 mV, -50 mV and -50 mV in female mice. Finally, TPNQ-sensitive whole-cell ROMK-currents in the DCT2 /initial-connecting tubule (CNT) were 910 pA (NK), 1,520 pA (5% KCl) and 1,540 pA (5% K-citrate) in male mice whereas the ROMK-mediated K currents were 1,005 pA, 1,590 pA and 1,570 pA in female mice. We conclude that the effect of HK intake on Kir4.1/Kir5.1 of the DCT and ROMK of DCT2/CNT is similar between male and female mice. Also, Cl content in HK diets has no effect on HK-induced inhibition of Kir4.1/Kir5.1 of the DCT and HK-induced stimulation of ROMK in DCT2/CNT.