Reactive oxygen species modulate neuronal excitability in rat intrinsic cardiac ganglia

Abstract

Reactive oxygen species (ROS) are produced as by-products of oxidative metabolism and occur in the heart during ischemia and coronary artery reperfusion. The effects of ROS on the electrophysiological properties of intracardiac neurons were investigated in the intracardiac ganglion (ICG) plexus in situ and in dissociated neurons from neonatal and adult rat hearts using the whole-cell patch clamp recording configuration. Bath application of ROS donors, hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) hyperpolarized, and increased the action potential duration of both neonatal and adult ICG neurons. This action was also recorded in ICG neurons in an adult in situ ganglion preparation. H2O2 and t-BHP also inhibited voltage-gated calcium channel (VGCC) currents and shifted the current–voltage (I–V) relationship to more hyperpolarized potentials. In contrast, H2O2 increased the amplitude of the delayed rectifier K+ current in neonatal ICG neurons. In neonatal ICG neurons, bath application of either superoxide dismutase (SOD) or catalase, scavengers of ROS, prior to H2O2 attenuated the hyperpolarizing shift but not the inhibition of VGCC by H2O2. In contrast, in adult ICG neurons, application of SOD alone had no effect upon either VGCC current amplitude or the I–V relationship, whereas application of SOD prior to H2O2 exposure abolished both the H2O2-mediated hyperpolarizing shift and inhibition. These data indicate that ROS alter depolarization-activated Ca2+ and K+ conductances which underlie neuronal excitability of ICG neurons. This affects action potential duration and therefore probably modifies autonomic control of the heart during ischemia/reperfusion.

Alterations of calcium channels and cell excitability in intracardiac ganglion neurons from type 2 diabetic rats

“…It is possible that one or multifactors (hyperglycemia, hyperlipidemia, and insulin resistance) induce the ROS overproduction and the latter is involved in the T2DM-induced changes of Ca 2ϩ channels and cell excitability in the ICG neurons. However, the further studies used with multifaceted technical approaches (from whole-animal to cellular-molecular levels) are needed because 1) we do not know whether T2DM induces overproduction of the ROS in the ICG neurons and 2) the above study (52) only investigated ROS-induced acute influence on the cell electrophysiological properties but not the chronic modulation on the mRNA and protein expressions of ion channels.…”

“…Multifactors (such as genetic, nutritional, and environmental factors) determine the etiology and development of T2DM, which induces hyperglycemia, hyperlipidemia, and insulin resistance. An electrophysiological study has shown that reactive oxygen species (ROS) can decrease the cell excitability of rat ICG neurons (52). It is possible that one or multifactors (hyperglycemia, hyperlipidemia, and insulin resistance) induce the ROS overproduction and the latter is involved in the T2DM-induced changes of Ca 2ϩ channels and cell excitability in the ICG neurons.…”

A Comparison of the Effects of Cumene Hydroperoxide and Hydrogen Peroxide on Retzius Nerve Cells of the Leech <i>Haemopis sanguisuga</i>

“…it is thus suggested that the intracellular application of H 2 o 2 decreases the open probability of BK(ca) at a low concentration (<1 mM), and increases or decreases the open probability of BK(ca) at a high concentration (5 mM). a recent paper reported that RoS donors (H 2 o 2 and t-BHP) reduced the voltage-operated ca 2+ current but increased the amplitude of the delayed rectifier K + current in adult rat intracardiac ganglion neurons [7,35].…”

Effects of Oxidative Stress on the Electrophysiological Function of Neuronal Membranes

“…Vega-Saenz de Miera and Rudy (1992) reported that H 2 O 2 inhibited three cloned voltagegated K + channels expressed in Xenopus oocytes. A recent paper reported that ROS donors (H 2 O 2 and t-BHP) reduced the voltage operated Ca 2+ current but increased the amplitude of the delayed rectifier K + current in adult rat intracardiac ganglion neurons (Dyavanapalli et al, 2010;Whyte et al, 2009). Nakaya et al (1992 ) examined the mechanism of membrane depolarization induced by CHP in guinea-pig papillary muscles, using ion-selective microelectrode and patch clamp techniques.…”