K+ modulation of microglial superoxide production: involvement of voltage-gated Ca2+ channels

A variety of cytoactive factors produced during injury and inflammation are known to activate the central nervous system (CNS) macrophage, the microglia. Since extracellular potassium levels are known to rise rapidly at sites of injury in the CNS, we examined the possibility that changes in extracellular potassium could mediate changes in microglial function. The effect of an increase in potassium concentration on microglial superoxide anion production was studied in cultured neonatal rat microglia. Rather than directly inducing superoxide anion production, exposure to media containing 25 and 55 mM potassium enhanced the production of superoxide induced by phorbol 12-myristate 13-acetate. This potentiation was blocked by nifedipine, a voltage-gated calcium channel blocker. Treatment of the microglia with BAY K 8644, an agonist for voltage-gated calcium channels, produced an enhancement of superoxide levels similar to that of potassium. Because these data indicated the presence of a voltage-gated calcium channel, we also examined whole cell current in cultured microglia. A small, voltage-dependent inward calcium current was seen that was increased by exposure of the microglia to BAY K 8644. The presence of a small but finite calcium influx via these channels may be an important factor in the regulation of intracellular microglial events such as activation of the NADPH oxidase and the consequent production of superoxide anion.

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Thiopental and Methohexital Depress Ca2+Entry into and Glutamate Release from Cultured Neurons

Anesthesiology ◽

10.1097/00000542-199806000-00029 ◽

1998 ◽

Vol 88 (6) ◽

pp. 1643-1653 ◽

Cited By ~ 17

Author(s):

Ning Miao ◽

Kaoru Nagao ◽

Carl Lynch

Keyword(s):

Calcium Channel ◽

Glutamate Release ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Neonatal Rat ◽

Reduced Form ◽

Dependent Manner ◽

Protective Effects ◽

Voltage Gated ◽

Voltage Gated Calcium Channel ◽

Dose Dependent

Background Although barbiturates activate alpha-aminobutyric acid type A receptors as part of their hypnotic effect, these drugs also inhibit voltage-gated calcium channels. The authors determined if barbiturates could decrease neuronal intracellular Ca2+ transients and the resulting glutamate release. Methods Neonatal rat cerebellar granule neurons were isolated and cultured on coverslips and studied at 37 degrees C. Spectrofluorometric assays were used during identical conditions to monitor intracellular Ca2+ with the Ca2+ -sensitive fluorophore fura-2 and glutamate release by a glutamate dehydrogenase-coupled assay, which produced the reduced form of nicotinamide-adenine dinucleotide phosphate in proportion to the amount of glutamate released. Neurons were depolarized by a rapid increase in external [K+] from 5 to 55 mM. Control responses were compared with those in the presence of 10, 30, and 100 microM thiopental; 3, 10, and 30 microM methohexital; decreased external [Ca2+]; or voltage-gated calcium channel blockers. Results Thiopental and methohexital depressed the intracellular Ca2+ transient peak and plateau in a dose-dependent manner, as did decreased Ca2+. The intermediate dose of either drug caused approximately 50% decrease in peak intracellular Ca2+ and 60% decrease in glutamate release. In the presence of specific L- and/or N-type voltage-gated calcium channel blockade by nicardipine or omega-conotoxin-GVIA, respectively, 30 microM thiopental further decreased the intracellular Ca2+ transient. Thiopental caused a dose-dependent decrease in glutamate release, which was proportional to the decreased peak intracellular Ca2+. Conclusions Thiopental and methohexital depress the depolarization-induced increase in intracellular Ca2+ and the accompanying glutamate release, actions which can contribute to the anesthetic and neuronal protective effects of these drugs.

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Effects of voltage-gated calcium channel subunit genes on calcium influx in culturedC. elegans mechanosensory neurons

Journal of Neurobiology ◽

10.1002/neu.20261 ◽

2006 ◽

Vol 66 (10) ◽

pp. 1125-1139 ◽

Cited By ~ 30

Author(s):

Christian Frøkjær-Jensen ◽

Katie S. Kindt ◽

Rex A. Kerr ◽

Hiroshi Suzuki ◽

Katya Melnik-Martinez ◽

...

Keyword(s):

Calcium Channel ◽

Calcium Influx ◽

Voltage Gated ◽

Mechanosensory Neurons ◽

Voltage Gated Calcium Channel

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Hyperosmotic regulation of voltage-gated calcium currents in rat anterior pituitary cells

Journal of Neurophysiology ◽

10.1152/jn.1996.75.5.1894 ◽

1996 ◽

Vol 75 (5) ◽

pp. 1894-1900 ◽

Cited By ~ 7

Author(s):

O. Matzner ◽

S. Ben-Tabou ◽

I. Nussinovitch

Keyword(s):

Calcium Channel ◽

Anterior Pituitary ◽

Calcium Influx ◽

Hormone Secretion ◽

Bay K 8644 ◽

Calcium Currents ◽

Pituitary Cells ◽

Activation Curve ◽

Voltage Gated ◽

Channel Agonist

1. The sensitivity of voltage-gated calcium currents to hyperosmotic media containing mannitol or sucrose (373-723 mOsm) and to the dihydropyridine (DHP) calcium channel agonist Bay K 8644 was examined in enriched populations of rat anterior pituitary somatotrophs by using the whole cell mode of the patch-clamp technique. 2. Hyperosmotic media reduced the amplitude of voltage-gated calcium currents. With a 61.9% increase in extracellular medium osmolarity (523 mOsm), low voltage-activated (LVA) calcium currents were reduced to 67.9 +/- 17.8% of control size and high voltage-activated (HVA) calcium currents were reduced to 57.0 +/- 5.7% (mean +/- SD) of control size. The hyperosmotic suppression of HVA calcium currents was usually accompanied with a negative shift of 6.0 +/- 2.9 mV (mean +/- SD) in the activation curve of HVA currents. 3. The DHP calcium-channel agonist Bay K 8644 (10 microM), which stimulates hormone secretion from somatotrophs, increased the amplitude of HVA calcium currents to 212.6 +/- 67.2% of their control size, prolonged their tail currents, and negatively shifted the activation curve of HVA calcium currents by 6.2 +/- 2.8 mV. 4. Hyperosmotic media reduced the amplitude of DHP-sensitive HVA calcium currents and their associated prolonged tail currents, thus providing direct evidence for hyperosmotic suppression of DHP-sensitive currents. 5. Hence, exposure of pituitary cells to hyperosmotic media reduced voltage-sensitive calcium influx through LVA and DHP-sensitive HVA calcium channels. The inhibition of calcium influx through DHP-sensitive channels, which are implicated in regulation of hormone secretion in these cells, suggests that inhibitory hyperosmotic effects on hormone secretion from pituitary cells may stem from inhibition of calcium influx, before the exocytotic process. These results may also be relevant to effects of hypertonicity on neurosecretion in the nervous system.

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