Oxidation Regulates Cloned Neuronal Voltage-Dependent Ca²⁺Channels Expressed inXenopusOocytes

Abstract

Functional modifications of neuronal P/Q-type voltagedependent Ca 2ϩ channels expressed in Xenopus oocytes by oxidation were examined electrophysiologically. Oxidation by external H 2 O 2 enhanced the whole-oocyte currents through the Ca 2ϩ channels composed of the ␣1A, ␣2/␦, and ␤3 subunits at negative voltages (Ͻ0 mV) without markedly affecting the currents at more positive voltages. Single-channel analysis showed that oxidation accelerates the overall channel opening process. The effect of H 2 O 2 to enhance the Ca 2ϩ channel activity did not require heterologous expression of the ␣2/␦ subunit, and it was not mimicked by a cysteine-specific oxidizing agent. The results suggest that oxidative stress may regulate the activity of neuronal Ca 2ϩ channels and that regulation by oxidation may be important in some clinical situations, such as in reperfusion injury after ischemic episodes.

Nox2, Ca 2+ , and Protein Kinase C Play a Role in Angiotensin II-Induced Free Radical Production in Nucleus Tractus Solitarius

“…25,34,40,55,56 The present data are consistent with previous reports that the elevation of intracellular Ca 2ϩ induced by Ang II is secondary to the action of ROS on L-type voltage-gated Ca 2ϩ channels. 25,34 However, the mechanisms underlying the effects of Nox2-derived ROS on voltage-gated Ca 2ϩ influx remain unclear.…”

“…Indeed, it is well established that ROS increase voltage-gated Ca 2ϩ currents in neurons. 55 Our finding that H 2 O 2 mimics the effect of Ang II on Ca 2ϩ currents in dmNTS neurons supports this possibility, albeit indirectly.…”

NADPH Oxidase Contributes to Angiotensin II Signaling in the Nucleus Tractus Solitarius

“…This finding is consistent with the report that ROS, especially superoxide, enhance Ca 2ϩ currents only at negative depolarizing voltages (Li et al, 1998;Annunziato et al, 2002); however, the mechanisms by which ROS alter Ca 2ϩ channel activities remain poorly understood (Kourie, 1998). One possibility is that ROS produce oxidation of sulfhydryl groups of cystine residues, resulting in the formation of disulfide bonds (S-S) that modify the structure-function relationship of Ca 2ϩ channel proteins (Chiamvimonvat et al, 1995;Kourie, 1998;Li et al, 1998). Another possibility is that ROS lead to peroxidation of membrane phospholipids, altering the structure of the channel proteins and their ionic conductance (Kourie, 1998).…”

Baroreflex function in conscious rats submitted to iron overload

“…Extensive reviews about the effect of iron, even at low concentrations, on free radicals and calcium homeostasis are available (26)(27)(28)(29). A dose-dependent effect of oxidative damage in rats submitted to the iron overload paradigm (30) agrees with our findings of the stronger cardiovascular effects encountered in TIO rats.…”

“…Both ferrous ions (Fe 2+ ) and free radicals have been associated with the impairment and breakdown of Ca 2+ -ATPase proteins in the sarcoplasmic reticulum of the rat heart (26). Oxidative stress has been suggested to enhance calcium currents through neuronal Ca 2+ channels (27). The heart has a high density of L-type Ca 2+ channels, which are directly modulated by Fe 2+ ions (28).…”