Role of calcium channel subtypes in calcium transients in hippocampal CA3 neurons

To examine the role of Go in modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of Gαo. In CA3 neurons from Gαo −/− mice, 2-chloro-adenosine and the GABAB-receptor agonist baclofen activated inwardly rectifying K+ currents and inhibited voltage-dependent Ca2+ currents just as effectively as in Gαo +/+ littermates. However, the kinetics of transmitter action were dramatically altered in Gαo −/− mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from Gαo −/− mice [time constant of 12.0 ± 0.8 (SE) s] than in neurons from Gαo +/+ mice (time constant of 2.6 ± 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2-chloro-adenosine on Ca2+ currents and K+currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking Gαo, some inhibition of Ca2+ currents by baclofen remained after NEM treatment, whereas baclofen activation of K+ currents and both effects of 2-chloro-adenosine were abolished. These results show that modulation of Ca2+ and K+ currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for Gαo. However, modulation is changed in the absence of Gαo in having much slower recovery kinetics. A likely possibility is that the very abundant Gαo is normally used but, when absent, can readily be replaced by G proteins with different properties.

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Voltage-dependent Calcium Channel Abnormalities in Hippocampal CA3 Neurons of Spontaneously Epileptic Rats

Epilepsia ◽

10.1111/j.1528-1167.2007.00957.x ◽

2007 ◽

Vol 48 (4) ◽

pp. 758-764 ◽

Cited By ~ 13

Author(s):

Hai-Dun Yan ◽

Kumatoshi Ishihara ◽

Ryosuke Hanaya ◽

Kaoru Kurisu ◽

Tadao Serikawa ◽

...

Keyword(s):

Calcium Channel ◽

Voltage Dependent Calcium Channel ◽

Voltage Dependent ◽

Hippocampal Ca3 ◽

Ca3 Neurons

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C2-P-04The role of hippocampal CA3 neurons as a homeostatic volume control

Microscopy ◽

10.1093/jmicro/dfv300 ◽

2015 ◽

Vol 64 (suppl 1) ◽

pp. i124.2-i124

Author(s):

Sang Hoon Lee ◽

Kea Joo Lee

Keyword(s):

Volume Control ◽

Hippocampal Ca3 ◽

Ca3 Neurons

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Calcium transients associated with the T type calcium current in myotubes.

The Journal of General Physiology ◽

10.1085/jgp.104.6.1113 ◽

1994 ◽

Vol 104 (6) ◽

pp. 1113-1128 ◽

Cited By ~ 16

Author(s):

J García ◽

K G Beam

Keyword(s):

Calcium Channel ◽

Calcium Current ◽

Time Course ◽

Calcium Transient ◽

Voltage Sensor ◽

Calcium Currents ◽

Calcium Transients ◽

Patch Clamp Technique ◽

In Cells

Immature skeletal muscle cells, both in vivo and in vitro, express a high density of T type calcium current and a relatively low density of the dihydropyridine receptor, the protein thought to function as the Islow calcium channel and as the voltage sensor for excitation-contraction coupling. Although the role of the voltage sensor in eliciting elevations of myoplasmic, free calcium (calcium transients) has been examined, the role of the T type current has not. In this study we examined calcium transients associated with the T type current in cultured myotubes from normal and dysgenic mice, using the whole cell configuration of the patch clamp technique in conjunction with the calcium indicator dye Fluo-3. In both normal and dysgenic myotubes, the T type current was activated by weak depolarizations and was maximal for test pulses to approximately -20 mV. In normal myotubes that displayed T type calcium current, the calcium transient followed the amplitude and the integral of the current at low membrane potentials (-40 to -20 mV) but not at high potentials, where the calcium transient is caused by SR calcium release. The amplitude of the calcium transient for a pulse to -20 mV measured at 15 ms after depolarization represented, on average, 4.26 +/- 0.68% (n = 19) of the maximum amplitude of the calcium transient elicited by strong, 15-ms test depolarizations. In dysgenic myotubes, the calcium transient followed the integral of the calcium current at all test potentials, in cells expressing only T type current as well as in cells possessing both T type current and the L type current Idys. Moreover, the calcium transient also followed the amplitude and time course of current in dysgenic myotubes expressing the cardiac, DHP-sensitive calcium channel. Thus, in those cases where the transient appears to be a consequence of calcium entry, it has the same time course as the integral of the calcium current. Inactivation of the T type calcium current with 1-s prepulses, or block of the current by the addition of amiloride (0.3-1.0 mM) caused a reduction in the calcium transient which was similar in normal and dysgenic myotubes. To allow calculation of expected changes of intracellular calcium in response to influx, myotubes were converted to a roughly spherical shape (myoballs) by adding 0.5 microM colchicine to culture dishes of normal cells. Calcium currents and calcium transients recorded from myoballs were similar to those in normal myotubes.(ABSTRACT TRUNCATED AT 250 WORDS)

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The Role of Calcium and the L-Type Calcium Channel in Pathological Remodeling of the Heart

Vascular Disease Prevention ◽

10.2174/1567270000805010013 ◽

2008 ◽

Vol 5 (1) ◽

pp. 104-115 ◽

Cited By ~ 1

Author(s):

Helena M. Viola ◽

Livia C. Hool

Keyword(s):

Calcium Channel ◽

Pathological Remodeling

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Epithelial expression and role of secreted STC1 on asthma airway hyperresponsiveness through calcium channel modulation

Allergy ◽

10.1111/all.14727 ◽

2020 ◽

Author(s):

Jiayan Xu ◽

Yaqi Meng ◽

Man Jia ◽

Jie Jiang ◽

Yi Yang ◽

...

Keyword(s):

Calcium Channel ◽

Airway Hyperresponsiveness ◽

Channel Modulation

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Neurotrophic factor-α1, a novel tropin is critical for the prevention of stress-induced hippocampal CA3 cell death and cognitive dysfunction in mice: comparison to BDNF

Translational Psychiatry ◽

10.1038/s41398-020-01112-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lan Xiao ◽

Vinay Kumar Sharma ◽

Leila Toulabi ◽

Xuyu Yang ◽

Cheol Lee ◽

...

Keyword(s):

Cell Death ◽

Learning And Memory ◽

Cognitive Dysfunction ◽

Neurotrophic Factor ◽

Maternal Separation ◽

Pyramidal Neurons ◽

Neuroprotective Activity ◽

Weaning Stress ◽

Hippocampal Ca3 ◽

Ca3 Neurons

AbstractStress leads to brain pathology including hippocampal degeneration, cognitive dysfunction, and potential mood disorders. Hippocampal CA3, a most stress-vulnerable region, consists of pyramidal neurons that regulate cognitive functions e.g. learning and memory. These CA3 neurons express high levels of the neuroprotective protein, neurotrophic factor-α1 (NF-α1), also known as carboxypeptidase E (CPE), and receive contacts from granule cell projections that release BDNF which has neuroprotective activity. Whether NF-α1-CPE and/or BDNF are critical in protecting these CA3 neurons against severe stress-induced cell death is unknown. Here we show that social combined with the physical stress of maternal separation, ear tagging, and tail snipping at weaning in 3-week-old mice lacking NF-α1-CPE, led to complete hippocampal CA3 degeneration, despite having BDNF and active phosphorylated TrkB receptor levels similar to WT animals. Mice administered TrkB inhibitor, ANA12 which blocked TrkB phosphorylation showed no degeneration of the CA3 neurons after the weaning stress paradigm. Furthermore, transgenic knock-in mice expressing CPE-E342Q, an enzymatically inactive form, replacing NF-α1-CPE, showed no CA3 degeneration and exhibited normal learning and memory after the weaning stress, unlike NF-α1-CPE-KO mice. Mechanistically, we showed that radio-labeled NF-α1-CPE bound HT22 hippocampal cells in a saturable manner and with high affinity (Kd = 4.37 nM). Subsequently, treatment of the HT22cpe−/− cells with NF-α1-CPE or CPE-E342Q equivalently activated ERK signaling and increased BCL2 expression to protect these neurons against H2O2-or glutamate-induced cytotoxicity. Our findings show that NF-α1-CPE is more critical compared to BDNF in protecting CA3 pyramidal neurons against stress-induced cell death and cognitive dysfunction, independent of its enzymatic activity.

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