Inhibition of -Cell Sodium-Calcium Exchange Enhances Glucose-Dependent Elevations in Cytoplasmic Calcium

OBJECTIVE—The sodium-calcium exchanger isoform 1 (NCX1) regulates cytoplasmic calcium (Ca 2 c ) required for insulin secretion in -cells. NCX1 is alternatively spliced, resulting in the expression of splice variants in different tissues such as NCX1.3 and -1.7 in -cells. As pharmacological inhibitors of NCX1 splice variants are in development, the pharmacological profile of -cell NCX1.3 and -1.7 and the cellular effects of NCX1 inhibition were investigated. RESEARCH DESIGN AND METHODS—The patch-clamp technique was used to examine the pharmacological profile of the NCX1 inhibitor KB-R7943 on recombinant NCX1.3 and -1.7 activity. Ca 2 imaging and membrane capacitance were used to assess the effects of KB-R7943 on Ca 2 c and insulin secretion in