Forefront of Na⁺/Ca²⁺ Exchanger Studies: Physiology and Molecular Biology of Monovalent Cation Sensitivities in Na⁺/Ca²⁺ Exchangers

Abstract

Sensitivities of the reverse-mode Na⁺/Ca²⁺ exchange activity measured as the Na⁺_i-dependent Ca²⁺ uptake to extracellular monovalent cations K⁺, Li⁺, and Na⁺ were compared between the K⁺-dependent (NCKX2) and the K⁺-independent Na⁺/Ca²⁺ exchanger (NCX1) overexpressed in a fibroblast cell. Interestingly, the exchange activity of NCKX2 was not influenced by Li⁺ while it was increased by K⁺. On the contrary, the activity of NCX1 was increased by Li⁺. Thus, the cation sensitivities to K⁺ and Li⁺ markedly differed between NCKX2 and NCX1. In addition, Na⁺ exerted a significantly smaller inhibitory effect on the activity in NCKX2 than in NCX1. The Na⁺/Ca²⁺ exchange activities of NCKX2 and NCX1 are considered to be regulated differentially via the respective binding site domains that have distinct sensitivities to the external monovalent cations.