Effects of ATP and elevated K+ on K+ currents and intracellular Ca2+ in human microglia

McLarnon, James G.; Zhang, L; Goghari, Vikram; Lee, Y.B; Walz, Wolfgang; Krieger, Charles; Kim, S.U

doi:10.1016/s0306-4522(98)00491-6

Cited by 43 publications

(55 citation statements)

References 40 publications

(51 reference statements)

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“…In several experiments, whole-cell currents were recorded from human microglia plated for 2-4 days on plastic coverslips (McLarnon et al, 1997(McLarnon et al, , 1999. Pipettes were fabricated from Corning glass (#7052) and had resistance values of 3-5 M⍀ when filled with intracellular solution.…”

Section: Whole-cell Patch-clampmentioning

confidence: 99%

Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia

Khoo

Helm

Choi

et al. 2001

Glia

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The effects of extracellular acidification on Ca 2ϩ -dependent signaling pathways in human microglia were investigated using Ca 2ϩ -sensitive fluorescence microscopy. Adenosine triphosphate (ATP) was used to elicit Ca 2ϩ responses primarily dependent on the depletion of intracellular endoplasmic reticulum (ER) stores, while platelet-activating factor (PAF) was used to elicit responses primarily dependent on store-operated channel (SOC) influx of Ca 2ϩ . The duration of transient responses induced by ATP was not significantly different in standard physiological pH 7.4 (mean duration 30.2 Ϯ 2.5 s) or acidified pH 6.2 (mean duration 31.7 Ϯ 2.8 s) extracellular solutions. However, the time course of the PAF response at pH 7.4 was significantly reduced by 87% with external pH at 6.2. These results suggest that acidification of extracellular solutions inhibits SOC entry of Ca 2ϩ with little or no effect on depletion of ER stores. Changes of extracellular pH over the range from 8.6 to 6.2 during the development of a sustained SOC influx induced by PAF resulted in instantaneous modulation of SOC amplitude indicating a rapidly reversible effect of pH on this Ca 2ϩ pathway. Whole-cell patch clamp recordings showed external acidification blocked depolarization-activated outward K ϩ current indicating cellular depolarization may be involved in the acid pH inhibition. Since SOC mediated influx of Ca 2ϩ is strongly modulated by membrane potential, the electrophysiological data suggest that acidification may act to inhibit SOC by cellular depolarization. These results suggest that acidification observed during cerebral ischemia may alter microglial responses and functions. GLIA 36:22-30, 2001.

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Section: Whole-cell Patch-clampmentioning

confidence: 99%

Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia

Khoo

Helm

Choi

et al. 2001

Glia

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“…Activation of purinergic P 2X receptors inhibits P 2Y -mediated Ca 2+ influx in human microglia binding to P 2Y receptors may then be coupled to activation of Ca 2+ influx through store-operated channels [10,14]. In addition, for both rodent and human microglia, activation of the P 2Y pathway has been found to enhance an outward K + current [3,4,10,14].…”

Section: Researchmentioning

confidence: 99%

“…Among the spectrum of stimuli found to elicit transient Ca 2+ responses in cultured rodent cells are complement [1], ATP [2][3][4], carbachol [5], platelet-activating factor (PAF [6]) and endothelin [7]. All of these stimuli (complement has not yet been tested) have also been found to cause transient Ca 2+ responses in human microglia [8][9][10][11]. It is important to note that differences between properties of rodent and human microglia have been reported such as the expression of inducible NOS by rodent, but not human, microglia [12].…”

Section: Introductionmentioning

confidence: 99%

“…The expression of purinergic receptor subtypes P 2X and P 2Y have been well documented in microglia [4,10,13,14]. In addition a P 2Z receptor, associated with a high conductance pore permeable to large hydrophylic solutes, has also been reported in microglia [15,16]; activation of this receptor may require concentrations of ATP near 1 mM [16].…”

Section: Introductionmentioning

confidence: 99%

“…In addition a P 2Z receptor, associated with a high conductance pore permeable to large hydrophylic solutes, has also been reported in microglia [15,16]; activation of this receptor may require concentrations of ATP near 1 mM [16]. The P 2X purinoceptor is coupled to a non-selective cationic channel allowing influx of Na + and Ca 2+ leading to a transient cell depolarization [14], whereas activation of the P 2Y purinoceptor leads to an increase in cytoplasmic [Ca 2+ ] due to emptying of IP 3 -sensitive intracellular stores [10,14]. Depletion of intracellular stores following ATP…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Activation of purinergic P2X receptors inhibits P2Y-mediated Ca2+ influx in human microglia

Wang

Kim²,

Breemen

et al. 2000

Cell Calcium

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Characterization of leukocyte subtypes in chicken inner ear sensory epithelia

O'Halloran

Oesterle

2004

J of Comparative Neurology

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Human hearing and balance require intact inner ear sensory hair cells, which transduce mechanical stimuli into electrical signals that are transmitted to the brain. Loss of hair cells after birth in mammals is irreversible, whereas birds are able to regenerate hair cells after insult and demonstrate ongoing hair cell production in the vestibular epithelia. Leukocytes reside in undamaged sensory epithelia of the avian inner ear and increase in number after trauma, prior to the proliferation of hair cell progenitors. It has been hypothesized that leukocyte-produced growth factors or cytokines may be involved in triggering hair cell regeneration. Little is known about the specific leukocyte subtypes present in avian ear. Immunohistochemistry with a panel of monoclonal antibodies to chicken leukocytes was used to identify leukocyte subtypes in normal posthatch chicken ear sensory epithelia. The responsiveness of the leukocytes to aminoglycoside-induced damage was also observed. Based on immunocytochemical and morphological criteria, we quantified leukocyte subtypes in normal and drug-damaged auditory and vestibular sensory epithelia. Data indicate that lymphocytes (B and T cells) do not reside in normal or drug-damaged ear sensory epithelia at 1-3 days post insult but are present in adjacent nonsensory tissues. The most common leukocytes in inner ear sensory epithelia are ramified cells of the myeloid lineage. Many of these are MHC class II positive, and a small percentage are mature tissue macrophages. An absence of leukocytes in lesioned areas of the auditory sensory epithelium suggests they may not play a critical role in triggering hair cell regeneration.

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Effects of ATP and elevated K+ on K+ currents and intracellular Ca2+ in human microglia

Cited by 43 publications

References 40 publications

Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia

Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia

Activation of purinergic P2X receptors inhibits P2Y-mediated Ca2+ influx in human microglia

Characterization of leukocyte subtypes in chicken inner ear sensory epithelia

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Effects of ATP and elevated K+ on K+ currents and intracellular Ca2+ in human microglia

Cited by 43 publications

References 40 publications

Inhibition of store‐operated Ca2+ influx by acidic extracellular pH in cultured human microglia

Inhibition of store‐operated Ca2+ influx by acidic extracellular pH in cultured human microglia

Activation of purinergic P2X receptors inhibits P2Y-mediated Ca2+ influx in human microglia

Characterization of leukocyte subtypes in chicken inner ear sensory epithelia

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Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia

Inhibition of store‐operated Ca²⁺ influx by acidic extracellular pH in cultured human microglia