P106Loss of myocardial nNOS in human atrial fibrillation (AF) shortens action potential duration (APD) by increasing Ito: Implications for AF-induced electrical remodelling

Purpose: Understanding the mechanism underlying atrial electrical remodelling in AF is of fundamental importance for the prevention and treatment of AF. We have recently found that neuronal nitric oxide synthase (nNOS) activity is dramatically reduced in atrial myocytes from patients with AF. Whether loss of nNOS activity contributes to AF-induced atrial electrical remodelling remains to be established. Methods: Whole-cell patch clamp was used to record action potentials (APs) and ion currents in human and murine right atrial myocytes. AF was induced in isoflurane anaesthetised mice by using trans-oesophageal electrical stimulation. N=number of patients or mice, n= number of myocytes. Results: Inhibition of nNOS by S-methylthiocitrulline (SMTC, 100 nM), induced a significant reduction in APD at 20 (38%), 50 (39%) and 90 (30%) percent of repolarization in atrial myocytes from patients in sinus rhythm (SR, N=8, n=38 control vs. N=8, n=31 in the presence SMTC, p