The transcription ?nuclear factor of activated T-cells? (NFAT) has a pivotal role in the development of cardiac hypertrophy and it is regulated via Ca(2+)-signal transductionpathways. Ionchannels of the TRPC-family are essentially involved in NFAT-regulation.Ca(2+)-influx via TRPC-channels promotes NFAT-dependent changes of cardiac gene expression patterns and simultaneously increases TRPC protein expression. In cardiac muscle cytosolic Ca(2+) performs two independent functions: (1) Ca(2+) is involved in cardiac excitation/contraction and (2) Ca(2+) is also involved in cardiac signal transduction as well as in cardiac gene expression. However, the consequences of increased TRPC-expression/-conductance on cardiac excitability remain widely unknown. The present study investigates the TRPC3-I/V-characteristics in the cardiac environment and the impact of the TRPC3-conductance on action potentials. Therefore the TRPC3-protein was overexpressed in the cardiac HL-1 cell system and the phenotype was assessed by patch-clamp- and Fura-2-technique. In HL-1 cells the TRPC3-mediated current shows the anticipated TRPC3-I/V-characteristic, but an unexpected exaggerated Ca(2+)-sensitivity. Consequently, a significant activation of the TRPC3-conductance was only observed in nominally-Ca(2+)-environment. TRPC3 overexpression shows neither influence on basal cell excitability, nor does it affect action potential properties of TRPC3-HL-1 cells. However, overexpression of TRPC3 increases receptor-mediated Ca(2+)-entry in HL-1 cells after Ca(2+)-re-addition. This TRPC3-dependent Ca(2+)-entry in HL-1 cells was validated via a permeationsdeficient/dominant-negative TRPC3-mutant. Therefore, increased TRPC3-proteine expression in HL-1 cells seems to be involved in intracellular Ca(2+) regulation but does not alter HL-1-cell excitability.