Muscarinic cholinergic suppression of ISO-stimulated ICa-L is absent in eNOSnull ventricular myocytes. The effects of ISO and CCh on L-type calcium current (ICa-L) in ventricular myocytes from both WT and eNOSnull mice are shown. (A) CCh significantly inhibited ISO-stimulated ICa-L in WT myocytes. Current traces labeled a, b, and c were recorded under control conditions (a), during ISO infusion (10 nM) (b), and during CCh infusions (10 μM) in the continuous presence of ISO (c). Averaged data for 21 cells is illustrated in the bar graphs. (B) CCh had no significant effect on ISO-stimulated ICa-L in ventricular myocytes from eNOSnull mice. Current traces were recorded under control conditions (a), during ISO infusion (b), during CCh infusion in the continuous presence of ISO (c), and during infusion of the NO donor S-nitroso-acetyl-cysteine (SNAC) (100 μM) in the presence of ISO and CCh. Note that direct application of NO caused a significant inhibition in ISO-stimulated ICa-L (d).