Reactive oxygen species alters the electrophysiological properties and raises [Ca²⁺]_iin intracardiac ganglion neurons

Abstract

We have investigated the effects of the reactive oxygen species (ROS) donors hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) on the intrinsic electrophysiological characteristics: ganglionic transmission and resting [Ca2+]i in neonate and adult rat intracardiac ganglion (ICG) neurons. Intracellular recordings were made using sharp microelectrodes filled with either 0.5 M KCl or Oregon Green 488 BAPTA-1, allowing recording of electrical properties and measurement of [Ca2+]i. H2O2 and t-BHP both hyperpolarized the resting membrane potential and reduced membrane resistance. In adult ICG neurons, the hyperpolarizing action of H2O2 was reversed fully by Ba2+ and partially by tetraethylammonium, muscarine, and linopirdine. H2O2 and t-BHP reduced the action potential afterhyperpolarization (AHP) amplitude but had no impact on either overshoot or AHP duration. ROS donors evoked an increase in discharge adaptation to long depolarizing current pulses. H2O2 blocked ganglionic transmission in most ICG neurons but did not alter nicotine-evoked depolarizations. By contrast, t-BHP had no significant action on ganglionic transmission. H2O2 and t-BHP increased resting intracellular Ca2+ levels to 1.6 ( ± 0.6, n = 11, P < 0.01) and 1.6 ( ± 0.3, n = 8, P < 0.001), respectively, of control value (1.0, ∼60 nM). The ROS scavenger catalase prevented the actions of H2O2, and this protection extended beyond the period of application. Superoxide dismutase partially shielded against the action of H2O2, but this was limited to the period of application. These data demonstrate that ROS decreases the excitability and ganglionic transmission of ICG neurons, attenuating parasympathetic control of the heart.

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].…”

Nicotinic Acetylcholine Receptors and Cardiac Vagal activity in Rats with Type 2 Diabetes

“…It is well documented that nAChRs, a sub-family of ligand-gated non-selective cation channels, mediate synaptic transmission in the peripheral autonomic ganglia [12,19]. On the postsynaptic membrane, activation of nAChRs by its agonists (such as ACh and nicotine) induces an inward current and eventually cause the terminal of postganglionic neurons to release neurotransmitter into the target organs [20][21][22][23][24][25]. In our present study, T2DM markedly decreased nAChR currents and the sensitivity of nAChR channels to nicotine in ICG neurons (Figure 3), which is probably involved in lower excitability of ICG neurons and blunted cardiac vagal activity in T2DM rats.…”

Autocrine/paracrine modulation of baroreceptor activity after antidromic stimulation of aortic depressor nerve in vivo

“…H 2 O 2 is produced in multiple cell types during periods of increased metabolic activity and participates in cell signaling in the nervous system (Saitoh et al, 2006; Gamper et al, 2006; Riquelme et al, 2011; Rice, 2011; Linley et al, 2012). It has been shown to hyperpolarize neurons and decrease neuronal excitability, primarily by increasing K + channel activity (Vega-Saenz de Miera & Rudy, 1992; Gamper et al, 2006; Dyavanapalli et al, 2010; Rice, 2011). Activity-induced oxidation of cysteine and/or methionine residues in K + channels has been proposed to provide negative feedback regulation of neuronal excitability (Hoshi & Heinemann, 2001; Gamper et al, 2006; Linley et al, 2012).…”