Role of Na⁺/Ca²⁺ Exchanger in the Initiation of Spontaneous Electrical Activity during Early Cardiogenesis

Abstract: Na⁺/Ca²⁺ exchanger (NCX) is the earliest functional genes in the developing mouse heart. It has been proposed to contribute to intracellular Ca²⁺ homeostasis and probably excitation-contraction coupling by electrogenic exchange of 1 intracellular Ca²⁺ ion for 3 extracellular Na⁺ ions. To date the functional expression of NCX and its correlation with the early spontaneous electrical activity during cardiogenesis are not thoroughly clarified. Using ES cell derived cardiomyocytes， we have found at very early development stage， NCX current (I_Na/Ca) is the major contributor of the caffeine (10 mmol/L) induced inward current at a constant holding potential of 35 mV as isomolar Li⁺ replacement of external Na⁺ blocked nearly 80% of the evoked inward current (n=8). NCX1 mRNA was identified in all these functionally measured cardiac cells using single-cell RT-PCR. Further functional relevance was investigated. The complete abolishment of membrane fluctuations and the intercalated action potentials (the earlier patterns of spontaneous electrical activity) by isomolar Li⁺ replacing external Na⁺ and Ni²⁺ (5 mmol/L) implicated the essentiality of NCX in the initiation of early membrane excitation. Thus we conclude that NCX1 is highly expressed even in very early stage cardiomycoytes and it plays a pivotal role in set-up of early spontaneous electrical activity.

CSTR: 32200.14.cjcb.2005.06.0013