FIG. 1.

Targeted disruption of the Ncx1 gene and Na/Ca exchange activity in Ncx1^+/+ and Ncx1^+/− islets. A: Structure of the WT and the targeted alleles. The eleventh exon, the neomycin resistance cassette, and the probes used in DNA and RNA hybridization analysis (bars underneath the targeted allele) are represented. B: DNA hybridization analysis of BamHI digested genomic DNA isolated from embryonic stem cell clones using the depicted probe. RH, recombinant homolog. C: PCR analysis for genotyping. D: Ncx1 mRNA levels in batches of islets from Ncx1^+/+ and Ncx1^+/− mice. GAPDH, glyceraldehyde-3-phosphate dehydrogenase. E: ⁴⁵Ca uptake in the presence and the absence of extracellular Na⁺. Means ± SEM of four experiments, comprising four to five replicates each. *P < 0.05, ***P < 0.001 vs. Na⁺ 139 mmol/L, #P < 0.001 vs. Ncx1^+/+. F: Effect of extracellular Na⁺ removal on [Ca²⁺]_i in Ncx1^+/+ and Ncx1^+/− islets. The period of exposure to Na⁺-free medium is indicated by a bar above the curves. The curves shown are the mean of seven traces in each case. G: Effect of KCl (50 mmol/L) on [Ca²⁺]_i in Ncx1^+/+ and Ncx1^+/− islets. The period of exposure to KCl is indicated by a bar above the curves. The curves shown are the mean of 13 traces in each case.