Adrenergic Facilitation of GABAergic Transmission in Rat Entorhinal Cortex

2007 ◽  
Vol 98 (5) ◽  
pp. 2868-2877 ◽  
Author(s):  
Saobo Lei ◽  
Pan-Yue Deng ◽  
James E. Porter ◽  
Hee-Sup Shin
Keyword(s):  
Entorhinal Cortex ◽  
Adrenergic Receptors ◽  
Gaba Release ◽  
Channel Blockers ◽  
Extracellular Solution ◽  
Gabaergic Transmission ◽  
Voltage Gated ◽  
Postsynaptic Currents ◽  
Kinase C ◽  
Gabaergic Function

Whereas the entorhinal cortex (EC) receives noradrenergic innervations from the locus coeruleus of the pons and expresses adrenergic receptors, the function of norepinephrine (NE) in the EC is still elusive. We examined the effects of NE on GABAA receptor–mediated synaptic transmission in the superficial layers of the EC. Application of NE dose-dependently increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from the principal neurons in layer II/III through activation of α1 adrenergic receptors. NE increased the frequency and not the amplitude of miniature IPSCs (mIPSCs) recorded in the presence of TTX, suggesting that NE increases presynaptic GABA release with no effects on postsynaptic GABAA receptors. Application of Ca2+ channel blockers (Cd2+ and Ni2+), omission of Ca2+ in the extracellular solution, or replacement of extracellular Na+ with N-methyl-d-glucamine (NMDG) failed to alter NE-induced increase in mIPSC frequency, suggesting that Ca2+ influx through voltage-gated Ca2+ or other cationic channels is not required. Application of BAPTA-AM, thapsigargin, and ryanodine did not change NE-induced increase in mIPSC frequency, suggesting that Ca2+ release from intracellular stores is not necessary for NE-induced increase in GABA release. Whereas α1 receptors are coupled to Gq/11 resulting in activation of the phospholipase C (PLC) pathway, NE-mediated facilitation of GABAergic transmission was independent of PLC, protein kinase C, and tyrosine kinase activities. Our results suggest that NE-mediated facilitation of GABAergic function contributes to its antiepileptic effects in the EC.

Adenosine A1 Receptor-Mediated Presynaptic Inhibition of GABAergic Transmission in Immature Rat Hippocampal CA1 Neurons

2003 ◽  
Vol 89 (3) ◽  
pp. 1214-1222 ◽  
Author(s):  
Hyo-Jin Jeong ◽  
Il-Sung Jang ◽  
Junichi Nabekura ◽  
Norio Akaike
Keyword(s):  
External Solution ◽  
Gaba Release ◽  
Inhibitory Effect ◽  
Channel Blockers ◽  
Gabaergic Transmission ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Cell Recording ◽  
Frequency Stimulation

In the mechanically dissociated rat hippocampal CA1 neurons with native presynaptic nerve endings, namely “synaptic bouton” preparation, the purinergic modulation of spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) was investigated using whole-cell recording mode under the voltage-clamp conditions. In immature neurons, adenosine (10 μM) reversibly decreased GABAergic mIPSC frequency without affecting the mean current amplitude. The inhibitory effect of adenosine transmission was completely blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), a selective Α1 receptor antagonist, and was mimicked by N 6-cyclopentyladenosine (CPA, 1 μM), a selective Α1 receptor agonist. However, CPA had no effect on GABAergic mIPSC frequency in postnatal 30 day neurons. N-ethylmaleimide (10 μM), a guanosine 5′-triphosphate binding protein uncoupler, and Ca2+-free external solution removed the CPA-induced inhibition of mIPSC frequency. K+ channel blockers, 4-aminopyridine (100 μM) and Ba2+ (1 mM), had no effect on the inhibitory effect of CPA on GABAergic mIPSC frequency. Stimulation of adenylyl cyclase with forskolin (10 μM) prevented the CPA action on GABAergic mIPSC frequency. Rp-cAMPS (100 μM), a selective PKA inhibitor, also blocked the CPA action. It was concluded that the activation of presynaptic Α1 receptors modulates the probability of spontaneous GABA release via cAMP- and protein kinase A dependent pathway. This Α1 receptor-mediated modulation of GABAergic transmission may play an important role in the regulation of excitability of immature hippocampal CA1 neurons.

scholarly journals Voltage-gated calcium channel blockers for psychiatric disorders: genomic reappraisal

2019 ◽  
Vol 216 (5) ◽  
pp. 250-253 ◽  
Author(s):  
Paul J. Harrison ◽  
Elizabeth M. Tunbridge ◽  
Annette C. Dolphin ◽  
Jeremy Hall
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Psychiatric Disorders ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Risk Genes ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Voltage Gated Calcium Channel ◽  
Second Use

SummaryWe reappraise the psychiatric potential of calcium channel blockers (CCBs). First, voltage-gated calcium channels are risk genes for several disorders. Second, use of CCBs is associated with altered psychiatric risks and outcomes. Third, research shows there is an opportunity for brain-selective CCBs, which are better suited to psychiatric indications.

Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering

1994 ◽  
Vol 71 (1) ◽  
pp. 1-10 ◽  
Author(s):  
S. A. Helekar ◽  
J. L. Noebels
Keyword(s):  
Gabaa Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Channel Blockers ◽  
Gamma Aminobutyric Acid ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Prolonged Duration ◽  
Ca3 Pyramidal Neurons ◽  
The Difference

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1–5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells

2018 ◽  
Vol 115 (51) ◽  
pp. E12083-E12090 ◽  
Author(s):  
Adam Bleckert ◽  
Chi Zhang ◽  
Maxwell H. Turner ◽  
David Koren ◽  
David M. Berson ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Selective Reduction ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Direction Selectivity ◽  
Inhibitory Synapses ◽  
Retinal Ganglion ◽  
Gabaergic Transmission ◽  
Starburst Amacrine Cells ◽  
Receptor Clusters

Synaptic inhibition controls a neuron’s output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on–off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC’s soma and dendrites could facilitate homeostatic control of the ooDSGC’s output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission.

scholarly journals T-type Ca2+channel modulation by otilonium bromide

2010 ◽  
Vol 298 (5) ◽  
pp. G706-G713 ◽  
Author(s):  
Peter R. Strege ◽  
Lei Sha ◽  
Arthur Beyder ◽  
Cheryl E. Bernard ◽  
Edward Perez-Reyes ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Contractile Activity ◽  
Clinical Effectiveness ◽  
Smooth Muscle Contraction ◽  
Hek293 Cells ◽  
Channel Blockers ◽  
Patch Clamp Technique ◽  
Extracellular Solution ◽  
Channel Modulation ◽  
Main Pathway

Antispasmodics are used clinically to treat a variety of gastrointestinal disorders by inhibition of smooth muscle contraction. The main pathway for smooth muscle Ca2+entry is through L-type channels; however, there is increasing evidence that T-type Ca2+channels also play a role in regulating contractility. Otilonium bromide, an antispasmodic, has previously been shown to inhibit L-type Ca2+channels and colonic contractile activity. The objective of this study was to determine whether otilonium bromide also inhibits T-type Ca2+channels. Whole cell currents were recorded by patch-clamp technique from HEK293 cells transfected with cDNAs encoding the T-type Ca2+channels, CaV3.1 (α1G), CaV3.2 (α1H), or CaV3.3 (α1I) alpha subunits. Extracellular solution was exchanged with otilonium bromide (10−8to 10−5M). Otilonium bromide reversibly blocked all T-type Ca2+channels with a significantly greater affinity for CaV3.3 than CaV3.1 or CaV3.2. Additionally, the drug slowed inactivation in CaV3.1 and CaV3.3. Inhibition of T-type Ca2+channels may contribute to inhibition of contractility by otilonium bromide. This may represent a new mechanism of action for antispasmodics and may contribute to the observed increased clinical effectiveness of antispasmodics compared with selective L-type Ca2+channel blockers.

Calcium From Internal Stores Triggers GABA Release From Retinal Amacrine Cells

2005 ◽  
Vol 94 (6) ◽  
pp. 4196-4208 ◽  
Author(s):  
Ajithkumar Warrier ◽  
Salvador Borges ◽  
David Dalcino ◽  
Cameron Walters ◽  
Martin Wilson
Keyword(s):  
Transmitter Release ◽  
Metabotropic Glutamate Receptor ◽  
Amacrine Cell ◽  
Ryanodine Receptors ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Voltage Gated ◽  
Metabotropic Glutamate ◽  
Inositol 1,4,5 Trisphosphate ◽  
Evoked Transmitter Release

The Ca2+ that promotes transmitter release is generally thought to enter presynaptic terminals through voltage-gated Ca2+channels. Using electrophysiology and Ca2+ imaging, we show that, in amacrine cell dendrites, at least some of the Ca2+ that triggers transmitter release comes from endoplasmic reticulum Ca2+ stores. We show that both inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) are present in these dendrites and both participate in the elevation of cytoplasmic [Ca2+] during the brief depolarization of a dendrite. Only the Ca2+ released through IP3Rs, however, seems to promote the release of transmitter. Antagonists for the IP3R reduced transmitter release, whereas RyR blockers had no effect. Application of an agonist for metabotropic glutamate receptor, known to liberate Ca2+ from internal stores, enhanced both spontaneous and evoked transmitter release.

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