Cholinergic protection against apoptosis in primary cardiac cells

The autonomic imbalance, characterized as the elevated sympathetic activity and the suppressed parasympathetic activity, is commonly present in a variety of cardiovascular diseases. However, the functional role of the parasympathetic suppression in cardiac pathology has not been well addressed. Our recent in vivo studies revealed that treatments with cholinergic reagents protected against cardiac dysfunction, while deficiency of M2 receptors increased cardiac susceptibility to stress. In this study, we further observed the cholinergic protection in primary cardiac cells. Pretreatments with cholinergic reagents reduced cell death induced by H2O2 and serum withdrawal. Furthermore, cholinergic treatments attenuated activity of caspase3/7, a central apoptotic signaling pathway. This cholinergic protection against cell death was associated with an enhanced ERK activation. These results suggest that the cholinergic direct effect against cell death may be one of the mechanisms of parasympathetic cardiac protection in cardiac diseases. This study was supported by American Heart Association Grant No. 0835256N, NIH COBRE grant No. 5 P20 RR017662, and INBRE Grant No. 2 P20 RR016479