Cholinergic regulation of contraction rhythm of spontaneously beating cardiac myocytes in culture

The cardiac sympathetic and parasympathetic nerves innervate the heart, and their activities modulate the heart rate. Previous studies have shown that cultured cardiac myocytes from neonatal rats have acetylcholine receptors (AchR) and their activation results in the decrease of spontaneous beating rates. Nitric oxide synthase (NOS) proteins are also expressed in cultured cardiac myocytes. However, physiological roles of nitric oxide (NO) in the autonomic regulation of contraction rhythm of cardiac myocytes remain unclear until now. In this study, we have tried to elucidate whether an NO signaling pathway is involved in the cholinergic regulation of contraction rhythm in cultured cardiac myocytes. Loading of myocytes with an agonist of acetylcholine receptors (carbachol) resulted in the decrease of beating rates, and such a suppressive effect was cancelled out by the treatment with an NOS inhibitor (L-NMMA) as well as with s scavenger of NO (carboxy-PTIO). These results suggest that the AchR-NOS-NO pathway is responsible for the regulation of contraction rhythm in cultured cardiac myocytes.