Voltage-Gated Calcium Channels Mediate Intracellular Calcium Increase in Weaver Dopaminergic Neurons During Stimulation of D2 and GABAB Receptors

2004 ◽  
Vol 92 (6) ◽  
pp. 3368-3374 ◽  
Author(s):  
Ezia Guatteo ◽  
C. Peter Bengtson ◽  
Giorgio Bernardi ◽  
Nicola B. Mercuri
Keyword(s):  
Calcium Channels ◽  
Dopaminergic Neurons ◽  
Calcium Influx ◽  
Dopamine Neurons ◽  
Gabab Receptors ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Whole Cell Patch Clamp ◽  
Midbrain Dopaminergic Neurons ◽  
And Control

The weaver ( wv) mutation affects the pore-forming region of the inwardly rectifying potassium channel (GIRK) leading to degeneration of cerebellar granule and midbrain dopaminergic neurons. The mutated channel ( wvGIRK) loses its potassium selectivity, allowing sodium (Na+) and possibly calcium ions (Ca2+) to enter the cell. Here we performed whole cell patch-clamp recordings combined with microfluorometry to investigate possible differences in calcium ([Ca2+]i) dynamics in native dopaminergic neurons (expressing the wvGIRK2 subunits) in the midbrain slice preparation from homozygous weaver ( wv/wv) and control (+/+) mice. Under resting conditions, [Ca2+]i was similar in wv/wv compared with +/+ neurons. Activation of wvGIRK2 channels by D2 and GABAB receptors increased [Ca2+]i in wv/wv neurons, whereas activation of wild-type channels decreased [Ca2+]i in +/+ neurons. The calcium rise in wv/wv neurons was abolished by antagonists of the voltage-gated calcium channels (VGCC); voltage clamp of the neuron at −60 mV; and hyperpolarization of the neuron to −80 mV or more, in current clamp, and was unaffected by TTX. Therefore we propose that wvGIRK2 channels in native dopamine neurons are not permeable to Ca2+, and when activated by D2 and GABAB receptors they mediate membrane depolarization and an indirect Ca2+ influx through VGCC rather than via wvGIRK2 channels. Such calcium influx may be the trigger for calcium-mediated excitotoxicity, responsible for selective neuronal death in weaver mice.

Inhibition of Dendritic Calcium Influx by Activation of G-Protein–Coupled Receptors in the Hippocampus

1997 ◽  
Vol 78 (6) ◽  
pp. 3484-3488 ◽  
Author(s):  
Huanmian Chen ◽  
Nevin A. Lambert
Keyword(s):  
Calcium Channels ◽  
Action Potential ◽  
G Protein ◽  
Pyramidal Neuron ◽  
Action Potentials ◽  
Calcium Influx ◽  
G Protein Coupled Receptors ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
G Protein Coupled

Chen, Huanmian and Nevin A. Lambert. Inhibition of dendritic calcium influx by activation of G-protein–coupled receptors in the hippocampus. J. Neurophysiol. 78: 3484–3488, 1997. Gi proteins inhibit voltage-gated calcium channels and activate inwardly rectifying K+ channels in hippocampal pyramidal neurons. The effect of activation of G-protein–coupled receptors on action potential-evoked calcium influx was examined in pyramidal neuron dendrites with optical and extracellular voltage recording. We tested the hypotheses that 1) activation of these receptors would inhibit calcium channels in dendrites; 2) hyperpolarization resulting from K+ channel activation would deinactivate low-threshold, T-type calcium channels on dendrites, increasing calcium influx mediated by these channels; and 3) activation of these receptors would inhibit propagation of action potentials into dendrites, and thus indirectly decrease calcium influx. Activation of adenosine receptors, which couple to Gi proteins, inhibited calcium influx in cell bodies and proximal dendrites without inhibiting action-potential propagation into the proximal dendrites. Inhibition of dendritic calcium influx was not changed in the presence of 50 μM nickel, which preferentially blocks T-type channels, suggesting influx through these channels is not increased by activation of G-proteins. Adenosine inhibited propagation of action potentials into the distal branches of pyramidal neuron dendrites, leading to a three- to fourfold greater inhibition of calcium influx in the distal dendrites than in the soma or proximal dendrites. These results suggest that voltage-gated calcium channels are inhibited in pyramidal neuron dendrites, as they are in cell bodies and terminals and thatG-protein–mediated inhibition of action-potential propagation can contribute substantially to inhibition of dendritic calcium influx.

scholarly journals Transthyretin oligomers induce calcium influx via voltage-gated calcium channels

2007 ◽  
Vol 100 (2) ◽  
pp. 446-457 ◽  
Author(s):  
Xu Hou ◽  
Helena C. Parkington ◽  
Harold A. Coleman ◽  
Adam Mechler ◽  
Lisandra L. Martin ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Influx ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

scholarly journals GABAB Receptors Couple to Potassium and Calcium Channels on Identified Lateral Perforant Pathway Projection Neurons

2000 ◽  
Vol 83 (2) ◽  
pp. 1073-1078 ◽  
Author(s):  
Xueyong Wang ◽  
Nevin A. Lambert
Keyword(s):  
Calcium Channels ◽  
Neurotransmitter Release ◽  
Granule Cells ◽  
Dorsal Hippocampus ◽  
Gabab Receptors ◽  
Projection Neurons ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Perforant Pathway ◽  
Inward Currents

Activation of presynaptic GABAB receptors inhibits neurotransmitter release at most cortical synapses, at least in part because of inhibition of voltage-gated calcium channels. One synapse where this is not the case is the lateral perforant pathway synapse onto dentate granule cells in the hippocampus. The current study was conducted to determine whether the neurons that make these synapses express GABAB receptors that can couple to ion channels. Perforant pathway projection neurons were labeled by injecting retrograde tracer into the dorsal hippocampus. The GABAB receptor agonist baclofen (10 μM) activated inwardly rectifying potassium channels and inhibited currents mediated by voltage-gated calcium channels in retrogradely labeled neurons in layer II of the lateral entorhinal cortex. These effects were reversed by coapplication of the selective GABAB receptor antagonist CGP 55845A (1 μM). Equivalent effects were produced by 100 μM adenosine, which inhibits neurotransmitter release at lateral perforant pathway synapses. The effects of baclofen and adenosine on inward currents were largely occlusive. These results suggest that the absence of GABAB receptor-mediated presynaptic inhibition at lateral perforant pathway synapses is not simply due to a failure to express these receptors and imply that GABAB receptors can either be selectively localized or regulated at terminal versus somatodendritic domains.

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