APPS November 2002 Meeting Abstract 2440

Reactive oxygen species (ROS) are produced as by-products of oxidative metabolism. ROS occur in the heart during ischaemia and coronary artery reperfusion, and have been implicated in cardiac dysfunction^1,2. The proximity of the intracardiac ganglia (ICG) to the coronary blood supply makes them susceptible to the effects of ROS and it has been shown that hypoxia and post-ischaemic reperfusion influence the neuronal firing activity of ICG³. The present study investigated the effects of ROS upon voltage-sensitive calcium channels (VSCCs) and the delayed rectifier potassium channel in isolated neurones of rat neonatal and adult ICG using the dialyzed whole-cell recording configuration of the patch clamp technique. Bath application of ROS donor, hydrogen peroxide (H₂O₂, 1 mM), inhibited the VSCC current and shifted the current-voltage (I-V) relationship to more hyperpolarized potentials in both neonatal and adult ICG. In contrast, H₂O₂increased the amplitude of the delayed rectifier potassium current in neonatal ICG. Bath application of superoxide dismutase (SOD, 100 U/ml), a scavenger of ROS, to neonatal ICG also inhibited the VSCC current and shifted the I-V relationship to more depolarized potentials. Furthermore, in neonatal ICG, application of SOD prior to H₂O₂attentuated the hyperpolarizing shift but not the inhibition of VSCC by H₂O₂. In contrast, in adult ICG, application of SOD alone had no effect upon either VSCC current amplitude or I-V relationship, but application of SOD prior to H₂O₂ abolished the hyperpolarizing shift and inhibition by H₂O₂. These data indicate that the effects of ROS alter depolarization-activated calcium and potassium conductances underlying neuronal excitability of ICG and therefore most likely modify autonomic control of the heart during ischaemia/reperfusion.