scholarly journals Multiple G-Protein βγ Combinations Produce Voltage-Dependent Inhibition of N-Type Calcium Channels in Rat Superior Cervical Ganglion Neurons

2000 ◽  
Vol 20 (6) ◽  
pp. 2183-2191 ◽  
Author(s):  
Victor Ruiz-Velasco ◽  
Stephen R. Ikeda
Keyword(s):  
Calcium Channels ◽  
G Protein ◽  
Superior Cervical Ganglion ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Cervical Ganglion ◽  
Ganglion Neurons

Neurotransmitters acting via different G proteins inhibit N-type calcium current by an identical mechanism in rat sympathetic neurons

1995 ◽  
Vol 74 (6) ◽  
pp. 2251-2257 ◽  
Author(s):  
I. Ehrlich ◽  
K. S. Elmslie
Keyword(s):  
Calcium Channels ◽  
G Protein ◽  
G Proteins ◽  
Calcium Current ◽  
Voltage Dependence ◽  
Sympathetic Neurons ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Kinetics Of

1. We studied the mechanism of voltage-dependent inhibition of N-type calcium current by norepinephrine (NE) and vasoactive intestinal peptide (VIP) in adult rat superior cervical ganglion (SCG) neurons using the whole cell patch-clamp technique. 2. The voltage dependence of inhibition is manifest in the reversal of inhibition by strong depolarization. We tested the hypothesis that this voltage dependence results from disruption of G proteins binding to calcium channels. According to this hypothesis, the kinetics of calcium current reinhibition following a strong depolarization should become faster for higher concentrations of active G proteins. 3. Assuming that larger inhibitions result from higher concentrations of active G proteins, we used different concentrations of NE to alter the amplitude of inhibition and, thus, the active G protein concentration. We found that the kinetics of reinhibition at -80 mV following a depolarizing pulse to +80 mV were faster for larger inhibitions. 4. VIP induces voltage-dependent inhibition of N-current via a different G protein (Gs) than that of NE (Go). We found that the effect of VIP on reinhibition kinetics was identical to that produced by NE. 5. Combined application of NE and VIP did not greatly increase the amplitude of the inhibition but significantly increased the rate of reinhibition. Thus NE plus VIP appear to greatly increase the concentration of the molecule binding to the channel (G protein according to the hypothesis). 6. The kinetics of calcium current disinhibition during strong depolarization (step to +80 mV) did not change with the size of the inhibition induced by NE, VIP or application of NE and VIP together. 7. Both the concentration-dependent reinhibition kinetics and concentration-independent disinhibition kinetics are consistent with the hypothesis that active G proteins bind directly to N-type calcium channels to modulate their activity in rat sympathetic neurons.

scholarly journals Differential Occurrence of Reluctant Openings in G-Protein–Inhibited N- and P/Q-Type Calcium Channels

2000 ◽  
Vol 115 (2) ◽  
pp. 175-192 ◽  
Author(s):  
Henry M. Colecraft ◽  
Parag G. Patil ◽  
David T. Yue
Keyword(s):  
Calcium Channels ◽  
G Protein ◽  
Action Potentials ◽  
Qualitative Difference ◽  
Hek 293 ◽  
Protein Inhibition ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Time Courses ◽  
Prepulse Facilitation

Voltage-dependent inhibition of N- and P/Q-type calcium channels by G proteins is crucial for presynaptic inhibition of neurotransmitter release, and may contribute importantly to short-term synaptic plasticity. Such calcium-channel modulation could thereby impact significantly the neuro-computational repertoire of neural networks. The differential modulation of N and P/Q channels could even further enrich their impact upon synaptic tuning. Here, we performed in-depth comparison of the G-protein inhibition of recombinant N and P/Q channels, expressed in HEK 293 cells with the m2 muscarinic receptor. While both channel types display classic features of G-protein modulation (kinetic slowing of activation, prepulse facilitation, and voltage dependence of inhibition), we confirmed previously reported quantitative differences, with N channels displaying stronger inhibition and greater relief of inhibition by prepulses. A more fundamental, qualitative difference in the modulation of these two channels was revealed by a modified tail-activation paradigm, as well as by a novel “slope” analysis method comparing time courses of slow activation and prepulse facilitation. The stark contrast in modulatory behavior can be understood within the context of the “willing–reluctant” model, in which binding of G-protein βγ subunits to channels induces a reluctant mode of gating, where stronger depolarization is required for opening. Our experiments suggest that only N channels could be opened in the reluctant mode, at voltages normally spanned by neuronal action potentials. By contrast, P/Q channels appear to remain closed, especially over these physiological voltages. Further, the differential occurrence of reluctant openings is not explained by differences in the rate of G-protein unbinding from the two channels. These two scenarios predict very different effects of G-protein inhibition on the waveform of Ca2+ entry during action potentials, with potentially important consequences for the timing and efficacy of synaptic transmission.

Relative contributions of G protein, channel, and receptor to voltage-dependent inhibition of neuronal N-type and P/Q-type calcium channels in HEK 293 cell lines

1997 ◽  
Vol 239 (2-3) ◽  
pp. 89-92 ◽  
Author(s):  
Brian A McCool ◽  
Michael M Harpold ◽  
Kenneth A Stauderman ◽  
Paul F Brust ◽  
David M Lovinger
Keyword(s):  
Calcium Channels ◽  
G Protein ◽  
Cell Lines ◽  
Hek 293 ◽  
Voltage Dependent ◽  
Dependent Inhibition ◽  
Protein Channel
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